Effects of social reorganization on cellular immunity in male cynomolgus monkeys

Exposure to acute stressors has been shown to impair cellular immunity in human beings and other animal species. Comparatively little is known, however, about the effects of long-term stressors on immune function and how individual behavioral characteristics may mediate differences in immune function and clinical disease susceptibility. To determine the effects of social stress on cellular immunity and reactivation of a latent herpesvirus, 20 Herpes B virus-positive male cynomolgus monkeys were exposed to four periodic reorganizations of social group memberships over 5 months. Observations were made to categorize individuals as high or low in expression of aggressive, fearful, and affiliative behaviors. Complete blood counts, lymphocyte proliferation tests, and natural killer cell cytotoxicity assays were performed immediately before and 4 days after reorganizations. Herpesvirus-specific immunoglobulin G antibody levels were measured, and oral and conjunctival swabs were cultured for virus. Reorganization was associated with increased lymphocyte counts (P = 0.0009) and decreased lymphocyte proliferation in response to phytohemagglutinin (P < 0.005), particularly among monkeys showing high levels of fear (P = 0.0137). High-aggressive monkeys showed lower baseline natural killer cell activity (P = 0.0013) and higher lymphocyte counts (P = 0.013) than low-aggressive monkeys. Herpesvirus antibody titers decreased over time (P < 0.004) and no positive virus cultures were obtained. Measures of cellular immunity and behavior were unrelated to virus-specific antibody titers. These results suggest that repeated exposure to a social stressor alters several measures of cellular immunity, and that some of these changes may be predicted by individual differences in agonistic behavior. In contrast to human studies, the results suggest that some psychological stressors may not cause reactivation of a common herpesvirus in this species. © 1996 Wiley-Liss, Inc.     

Mitogenic responses of peripheral blood mononuclear cells of vervet monkeys (Cercopithecus aethiops): Apparent role of adherent cells

Peripheral blood mononuclear cells (PBM) from normal vervet monkeys (Cercopithecus aethiops) were examined for blastogenic responses to concanavalin A (ConA), phytohemagglutinin (PHA), and pokeweed mitogen (PWM). The mitogen stimulated PBM in a dose-dependent manner. Response to ConA was apparently higher than for the other two mitogens. Cell density and mitogen concentration were critical parameters for optimal lymphocyte proliferation, an observation in line with that reported for other mammalian species. Depletion of an adherent cell population probably of monocyte/macrophage lineage from vervet PBM gave higher proliferative responses to both ConA and PHA, but the response without adherent cells to ConA was greater than the response without adherent cells to PHA. This latter finding is in contrast to what has been reported in many other species.     

Post-conflict affiliation in common marmosets (Callithrix jacchus jacchus)

Post-conflict (PC) affiliation has been demonstrated in a number of Old World monkeys and apes, but very little is known about the occurrence of the phenomenon in New World monkeys. This study examined 282 PC interactions after spontaneous conflicts around feeding time in two family groups (N = 12) of captive common marmosets, Callithrix jacchus jacchus. We found an overall corrected conciliatory tendency of 31%. Selective attraction was seen: former opponents met significantly more often in PCs than in matched controls (MCs) (27% and 16%, respectively). There was no difference in the occurrence of PC affiliation between dyads consisting of parent-offspring constellations compared to offspring-offspring constellations. PC affiliative behaviors were seen in the first three minutes following conflict termination, and consisted mainly of proximity, play invitations, and food transfer. Notably, former opponents remained within arm's reach after 17% of conflicts. Affiliation was more likely to follow after conflicts involving play issues. The functional importance of the PC affiliation in marmosets remains to be examined.     

Mitogen response of peripheral blood and splenic lymphocytes and effect of 2-mercaptoethanol in tumor-bearing mice

Summary A murine osteosarcoma in which the number of tumor cells can be continually monitored by measuring the circulating plasma alkaline phosphatase levels was used to determine the effect of tumor burden on peripheral blood and splenic lymphocyte response to mitogens. In animals with tumors of different sizes, the pattern of response of the peripheral blood lymphocytes (PBL) to mitogens is different from that of splenic lymphocytes. PBL response to ConA, PHA, and LPS was initially depressed, but response to PHA and LPS recovered later, as the tumor burden exceeded 6%. However, the recovery of LPS response was not consistent, in that recovery was not seen when the tumor burden was 5%–6%. Response to ConA remained depressed. Splenic lymphocytes showed progressive decline of PHA response. Treatment of tumor-bearing mice with 2-mercaptoethanol (2-ME) restored the ConA response of PBL in 56% of mice. Treatment with 2-ME did not restore PBL response to PHA or LPS. Abbreviations used in this paper: PBL, peripheral blood lymphocytes; peripheral blood lymphocytes; ConA, concanavalin A; PHA, phytohemagglutinin; LPS, lipopolysaccharide; 2-ME, 2-mercaptoethanol; FCS, fetal calf serum; AP, alkaline phosphatase; OS, osteosarcoma     

Aggression and social support predict long‐term cortisol levels in captive tufted capuchin monkeys (Cebus [Sapajus] apella)

Many nonhuman primates live in complex social groups in which they regularly encounter both social stressors such as aggression and social support such as that provided by long‐term affiliative relationships. Repeated exposure to social stressors may result in chronically elevated cortisol levels that can have deleterious physical effects such as impaired immune function, cardiovascular disease, and reduced brain function. In contrast, affiliative social relationships may act as a buffer, dampening the release of cortisol in response to acute and chronic stressors. Understanding how social stressors and social support predict cortisol levels is therefore essential to understanding how social situations relate to health and welfare. We studied this relationship in 16 socially housed captive brown capuchin monkeys (Cebus [Sapajus] apella) by comparing long‐term hair cortisol levels with behavioral measures of social stress (dominance rank, rank certainty, and amount of aggression received) and social support (amount of affiliation and centrality in the affiliative social network of the group). Dominance rank, rank certainty, amount of affiliation, and age were not significant predictors of long‐term cortisol levels in this population. Instead, long‐term cortisol levels were positively related to the amount of aggression received and negatively related to centrality in the affiliative social network of the group. This pattern may be attributed to the species’ socially tolerant dominance system and to the availability of social support across the dominance hierarchy.     

Influence of dietary lipids on agonistic and affiliative behavior in Macaca fascicularis

The current study evaluates the hypothesis, derived from previous investigations, that alterations in dietary fat and cholesterol influence the social behavior of monkeys. Subjects were 62 adult male, cynomolgus macaques (Macaca fascicularis) assigned originally to an investigation of atherosclerosis regression. This study thus involves a secondary analysis of data derived from an investigation conducted for another purpose. Animals were housed for 14 months' in social groups of five individuals each and initially fed a diet very high in saturated fat and cholesterol to induce coronary artery atherosclerosis. Monkeys were then exposed for 28 months to one of three conditions; (1) a moderately high-fat, high-cholesterol diet and an unstable social environment (in which monkeys were switched among groups monthly); (2) a low-fat, low-cholesterol diet and an unstable social environment; and (3) a low-fat, low-cholesterol diet and a stable social environment. A comparison of animals living in unstable groups revealed that those consuming the low-fat diet exhibited more overt aggression (P < 0.001) and overt submission (P < 0.01) than did monkeys eating the high-fat diet. A second comparison involved only those animals living in stable social units. These monkeys, while consuming the low-fat diet, engaged in more aggression and submission (P_s < 0.05), spent less time in passive body contact or within touching distance (P_s < 0.001), and spent more time alone (P < 0.001) than they had initially while consuming a very high-fat diet. The current investigation is the first on this topic to include measures of social behavior in animals both before and after a reduction in dietary fat. The findings that such a reduction is associated with increased agonism and decreased affiliation may help explain the epidemiologic association in human beings between low or reduced plasma cholesterol concentrations and a high incidence of violence-related mortality. More generally, the data are consistent with the hypothesis that there is a negative feedback adaptation providing for appropriate changes in behavior in response to periodic dietary privation. © 1996 Wiley-Liss, Inc.     

Sex hormones and immune dysregulation in multiple myeloma

A group of 49 multiple myeloma patients, 20 men and 29 women, were evaluated. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-oestradiol (E) and testosterone (T) serum concentrations have been detected by radioimmunoassay. Peripheral blood lymphocyte proliferation in response to phytohaemagglutinin (PHA), concanavalin A (ConA), recombinant interleukin-2 (rIL-2) and dextran sulphate (DxS) was investigated. Our findings provide evidence for two different patterns of sex hormone changes and immune dysfunctions presented differently by male and female multiple myeloma patients. In men increased FSH, LH and E concentrations and an augmented E to T ratio were associated with decreased lymphocyte blastogenic response to PHA, ConA and increased proliferation to rIL-2 and DxS. Female patients with multiple myeloma demonstrated normal values of FSH, LH and T, but a diminished E level and decreased E to T ratio correlated with a lymphocyte normal response to PHA and ConA and augmented blastogenesis to IL-2 and DxS. Our data, while admittedly preliminary, suffice to provide an indication of sex hormone changes in multiple myeloma patients, which could be responsible, at least in part, for the immune dysfunction observed in multiple myeloma.     

Application of Concanavalin A during immune responsiveness skin‐swelling tests facilitates measurement interpretation in mammalian ecology

The skin‐swelling test is a simple and widespread method used in field ecological research to estimate cellular immune responsiveness in animals. This immunoecological test is based on measuring the magnitude of tissue swelling response at specific times following subcutaneous application of an experimental pro‐inflammatory stimulant. In the vast majority of studies across vertebrate taxa, phytohemagglutinin (PHA) is used as a universal stimulant. Given the complexity of immune response activation pathways of PHA, however, interpretation of test results can be ambiguous. Goal of this study was to improve methodology of the skin‐swelling test to decrease this ambiguity. Here, we present an alternative protocol aimed at facilitating interpretation of skin‐swelling data for mammals. Based on previous evidence suggesting that mammalian T cells are readily activated by Concanavalin A (ConA) in vitro, we compared cellular immune responses in vivo to PHA and ConA as an alternative pro‐inflammatory stimulant in mice. We measured magnitude of tissue swelling and compared it with intensity of blood cell infiltration into tissue over a 72‐hour interval. Our results corroborate that PHA and ConA show important differences in both dynamics and response amplitude in rodents. ConA induces stronger swelling with a distinct leukocyte activity pattern and higher pro‐inflammatory cytokine (interleukin 6 [IL‐6] and interferon gamma[IFN‐γ]) expression than PHA during peak response (24‐h post‐treatment). Furthermore, unlike PHA, magnitude of swelling was positively associated with cellular activity (number of neutrophils infiltrating tissue) following ConA injection. We conclude that ConA is the more suitable stimulant for skin‐swelling tests in mammals. This is because of the molecular binding specificity in the two lectins, that is, ConA specifically activates T cells while PHA also triggers erythroagglutination. We propose that ConA be used in all future ecological testing in mammals as it exhibits better performance and its application facilitates immunological interpretation of skin‐swelling test results.     

Longitudinal cellular immune responses in asymptomatic and symptomatic Brugia malayi-infected Indian leaf monkey Presbytis entellus

To investigate the cell-mediated immune (CMI) responses of the host during the development of acute filarial disease manifestations, we studied the sequential changes in CD4+ and CD8+ T-cell subsets, leukocyte migration inhibition (LMI) response to Brugia malayi adult worm antigen, and concanavalin-A (ConA) and filarial antigen-induced lymphocyte transformation (LT) in the Indian leaf monkey (Presbytis entellus)-B. malayi model. Filarial infection was established in monkeys by subcutaneous inoculations of infective larvae (L3) (700-1,250 L3/monkey) in multiple doses, and the infected monkeys were categorized as symptomatic (Sym) and asymptomatic (Asym) depending on whether or not acute clinical manifestations were shown by them. In Sym monkeys, LMI response to homologous adult parasite antigen was significantly suppressed as compared to Asym monkeys. In Asym monkeys, LMI response varied among the animals; 2 showed an increase throughout the study period and 2 showed suppression at different time points. When compared with Asym monkeys, CD8+ T cells in Sym monkeys showed a trend of significant increase after day 180 postinoculation (PI). CD4+ T cells remained within the normal range till day 300 (PI), after which they showed a marginal increase. ConA-stimulated LT was suppressed in Asym monkeys from day 60 PI. Antigen-stimulated LT was unresponsive in both Asym and Sym animals. Thus, the host's LT response to ConA is suppressed in Asym animals, and alteration in CD8+ T-cell number and LMI response in Sym monkeys may be involved in the development of the acute disease manifestations in this model.     

Effect of chronic microwave radiation on T cell-mediated immunity in the rabbit

Experiments were conducted to elucidate the effects of chronic low power-level microwave radiation on the immunological systems of rabbits. Fourteen male Belgian white rabbits were exposed to microwave radiation at 5 mW/cm², 2.1 GHz, 3 h daily, 6 days/week for 3 months in two batches of 7 each in specially designed miniature anechoicchambers. Seven rabbits were subjected to sham exposure for identical duration. The microwave energy was provided through S band standard gain horns connected to a 4K3SJ2 Klystron power amplifier. The first batch of animals were assessed for T lymphocyte-mediated cellular immune response mechanisms and the second batch of animals for B lymphocyte-mediated humoral immune response mechanisms. The peripheral blood samples collected monthly during microwave/sham exposure and during follow-up (5/14 days after termination of exposures, in the second batch animals only) were analysed for T lymphocyte numbers and their mitogen responsiveness to ConA and PHA. Significant suppression of T lymphocyte numbers was noted in the microwave group at 2 months (P<0.01, % 21.5%) and during follow-up (P<0.01, % 30.2%). The first batch animals were initially sensitised with BCG and challenged with tuberculin (0.03 ml) at the termination of microwave irradiation/sham exposure and the increase in foot pad thickness ( mm), which is a measure of T cell-mediated immunity (delayed type hypersensitivity response, DTH) was noted in both the groups. The microwave group revealed a better response than the control group (%+12.4 vs.+7.54). The animals were sacrified and the tissue T lymphocyte counts (spleen and lymph node) were analysed. No significant variation was observed in the tissue T lymphocyte counts of microwave-irradiated rabbits. From these results it is speculated that the T lymphocytes are sequestered to various lymphoid organs under the influence of microwaves. A sub-population of T cells known as T helper cells (mediating DTH response) are probably not affected by microwave radiation. It is clear from our experiments that although chronic microwave radiation at 5 mW/cm² leads to suppression of peripheral T lymphocyte numbers, there is no concomitant functional impairment of these cells as evidenced by functional assays.     

Progressive loss in vitro immune response with tumor growth.

Peripheral blood lymphocytes from rats carrying a transplantable hepatoma were cultured in the presence of phytohemagglutinin (PHA), concanavalin A (ConA) or dextran sulfate (DS) at various times after tumor cell inoculation or after its surgical removal. Mitogen-induced lymphocyte transformation, measured by tritiated thymidine incorporation, declined as the tumor size increased, especially when cells were cultured in autologous serum. The response to PHA and ConA declined prior to the response to DS. This inhibition could not be removed by extensive washing of the cells, alteration of serum concentration, time of incubation or mitogen dose. Culture for 24 hr prior to the addition of high doses of mitogen resulted in partial restoration of the PHA and ConA, but not DS, responses. Previously inhibited responses also returned when the tumor was surgically removed. Spleen cells from animals with large tumors were also inhibited.     

Neighbor effects in marmosets: social contagion of agonism and affiliation in captive Callithrix jacchus

Researchers have demonstrated the neighbor effect for affiliative and agonistic neighbor vocalizations in captive chimpanzees. We extend the investigation of the neighbor effect to New World monkeys, Callithrix jacchus. We collected data on vocalizations and behaviors of 31 focal individuals and concurrent neighbor vocalization within three behavioral categories: intragroup and intergroup aggression and intragroup affiliation. We investigated whether there was an influence of neighbor vocalizations on focal behavior within the same behavioral category. For data analysis we used approximate randomization of paired‐sample t‐tests. We found that marmosets performed intergroup aggressive behavior (bristle, anogenital present for neighbor loud shrill only) for significantly longer, and emitted significantly more intergroup agonistic vocalizations (twitter, loud shrill), at a high frequency of intergroup agonistic neighbor vocalizations (twitter, loud shrill) than at low. The marmosets were also significantly more likely to engage in bristle behavior immediately after hearing a neighbor intergroup aggressive call (twitter, loud shrill) than directly beforehand. High neighbor intragroup agonistic calls (chatter) were associated with significantly longer spent in related behavior (composite of: attack, chase, steal food). Affiliative behaviors (share food, grooming invite) were engaged in by marmosets for significantly longer at higher frequencies of affiliative neighbor chirp calls than at low. Marmosets were also significantly more likely to perform food sharing and active affiliative contact immediately after rather than before hearing a neighbor chirp call. Our findings suggest that neighbor vocalizations influence marmoset behavior through social contagion and indicate that the neighbor effect for affiliation and aggression generalizes to the marmoset. Am. J. Primatol. 72:549–558, 2010. © 2010 Wiley‐Liss, Inc.     

The Immunological Responses of Marsupials

Recent work on the immune responses of marsupials is reviewed,with emphasis on cellular immune responses of the macropod marsupialSetonix brachyurus (quokka). Adult marsupials show immunologicalresponses broadly comparable to those of eutherian mammals.However, two immunological mechanisms have evolved to protectthe immunologically immature neonate: namely, the passive transferof antibody and the rapid maturation of immune competence. Thymectomyin marsupials causes a marked lymphocytic depletion of the lymphnodes and spleen, and, in the quokka, a transient abolitionof the humoral immune response to SRBC and depression of theresponse to other antigens. The blood leucocyte response tophytohemagglutinin (PHA) in vitro is also depressed. Althougha wasting syndrome does not occur in the quokka, neonatallythymectomized animals have a markedly reduced lifespan. Thymusgrafts in either intact or neonatally thymectomized pouch youngpersist, and in the latter case, fully reconstitute the in vitroleucocyte response to PHA. However, a concomitant restorationof the hemolytic antibody response was not achieved. A highlevel of lymphocyte chimaerism was found in the grafted animals.These results are discussed with reference to the specificityof cell-cell cooperation in the antibody response, and the possibleimplication of thymic humoral factors.     

The immunological status of breast cancer patients during treatment with a new antiestrogen,toremifene

Summary The immune status of breast cancer patients was followed during antiestrogen treatment for at least 1 year or until progression of the disease. Twelve postmenopausal women with advanced estrogen-receptor-positive breast cancer were treated with a novel antiestrogen, toremifene. Immune functions were determined before the start of the treatment and at 3, 6, and 12 months. For NK cell cytotoxicity testing there were 74 healthy controls and for T cell subset measurements 28 healthy controls. No statistically significant changes in the T cell subsets or NK cell cytotoxicity were observed during treatment. However, throughout toremifene treatment patients had fewer CD4 cells (T helper lymphocytes) than did the controls. Cancer patients had higher pretreatment B cell values than the controls,P = 0.01, but during the first months of toremifene treatment B cell values decreased and remained within the normal range thereafter. A positive effect on mitogen-stimulation tests with phytohemagglutinin (PHA) and concanavalin A (ConA) was observed during the first months of treatment (P = 0.01 for PHA and 0.03 for log [ConA] and a stabilization at the higher level thereafter. These results indicate that toremifene has a stimulatory effect on cell-mediated immunity in breast cancer patients.     

Studies on rabbit lymphocytes in vitro : XX. Demonstration of cells reactive to more than one mitogen by mixed sequential stimulation

Rabbit peripheral blood lymphocyte (PBL) cultures stimulated by ConA and then blocked by the addition of competing sugar or antiserum after 6–15 h of ConA prestimulation respond to restimulation by PHA or PWM to a much greater extent than to continuous stimulation or delayed stimulation with PHA or PWM. This effect of mixed lectin sequential stimulation indicates that many of the same PBLs will respond to more than one mitogen, but that some cells require preactivation by one mitogen in order to respond fully to another mitogen. Thus, the number of PBLs which respond to PHA or PWM alone is much less than the number which respond following pretreatment with ConA when the pretreatment effect of ConA alone is blocked. Rabbit PBLs do not respond to LPS and preactivation by ConA does not prepare rabbit PBLs to respond to LPS.     

Phenotypic and Functional Characterization of Lymphocytes from Different Age Groups of Bolivian Squirrel Monkeys (Saimiri boliviensis boliviensis)

Due to many physiological and genetic characteristic similarities to humans, squirrel monkeys provide an ideal animal model specifically for studying malaria, and transmissible spongiform encephalopathies (Creutzfeldt-Jacob disease). While squirrel monkeys three years and older are generally considered adult subjects suitable for use in medical research studies, little is known about the functional properties of lymphocytes in relation to the age of these animals, which could significantly impact the quality and quantity of innate and adaptive immune responses. In this study, we investigated differences in the phenotype and function of lymphocytes subsets of young (3–4 years), adult (8–10 years) and aged (16–19 years) squirrel monkeys. In general, animals in all three age groups exhibited comparable numbers of different lymphocyte subsets except for CD20+ B cells that were significantly lower in aged relative to young animals and T cells subsets expressing both CD4 and CD8 (double positive) were significantly higher in aged relative to young animals. With increasing age, phenotypic differences in central and effector memory T cells subsets were observed, that were more pronounced for the CD8+ T cells. Despite equal proportions of CD3+ T cells among the three age groups, responses of peripheral blood mononuclear cells to T cell mitogens PHA and Con A showed lower IFN-γ producing cells in the aged group than that in the young group. Furthermore, aged animals showed significantly higher plasma levels of inflammatory cytokines IL-6, IFN-γ, TNF-α, IL-10 and IL-12. These findings suggest that while the squirrel monkeys in general share phenotypic and functional similarities of lymphocyte subsets with humans in relation to age, specific differences exist in immune function of lymphocytes between young and old animals that could potentially impact experimental outcomes for which the measurement of immunologic endpoints are critical.     

Long-term follow-up of general immune competence in breast cancer

Summary Pre-treatment and sequential post-treatment (at 3 months, 6 months, 1, 2, 3, 4 and 5 years) examination of general immune competence was performed in 185 consecutive breast cancer patients. The patients were followed for 5 to 11 years to monitor the dynamic relationship between host immunity and cancer and to examine the effect of the treatment method. The tests of immune competence used were immunoglobulins IgG, IgA, IgM, leucocyte counts, percentage and total lymphocyte counts and Mantoux and DNCB skin hypersensitivity tests.Serum IgG and IgA showed no change relating to treatment method in recurrence-free patients; but IgG levels were higher when recurrent disease was imminent or established; IgM diminished (P<0.001) after treatment and this continued at 5 years in all patient groups. Simple lymphocyte counts showed the most interesting changes. They remained depressed for as long as 60 months following radiotherapy (P<0.01). After treatment by surgery, lymphocyte counts rose in patients without recurrence, but fell when systemic recurrence was imminent or established. This effect was not seen in patients with local recurrence only. There was no change in immune competence immediately before recurrence sufficient to be of clinical usefulness, but a low pre-treatment lymphocyte count with a steady rise after surgery carried a good prognosis. Similarly a high initial lymphocyte count with a fall after surgery was indicative of recurrence. Universal and prolonged depression of lymphocyte counts following radiotherapy was confirmed, and the effect was additive to that of tumour load in recurrent disease.Because of the large number of statistical calculations carried out, some of the apparently significant findings may be due to chance. However, the general trends emerging suggest that similar long-term studies, using the more sophisticated measures of lymphocyte function now available, might be rewarding.     

Immobilization of lymphocytes at surfaces by lectins

Phytohemagglutinin (PHA) and Concanavalin A (ConA) cause normal chicken lymphocytes to adhere to glass and plastic surfaces. Pokeweed mitogen (PWM) does not cause adherence. The effect of ConA was studied in detail. The reaction begins within 15 min at 25 °C and proceeds to completion by 2 h. It is independent of pH and resembles in this respect the spontaneous adherence which can occur in protein-depleted suspensions of chicken lymphocytes. It is distinguished from spontaneous adherence by conducting the reaction in 1% or more serum protein; high concentrations exert a slight restraint, which can be overcome by increasing the concentration of ConA. The reaction is slightly greater at high cell concentrations, is inhibited by 3 mM sodium cyanide, and is effectively blocked by 3 mM iodoacetamide and the α-methyl- -glycosides of glucose and mannose. The reaction is not affected by 2-deoxy- -glucose or N-acetyl glucosamine. Adherent lymphocytes detach when the lectin solution is replaced with lectin-free saline; they readhere when reexposed to ConA or to alloantibody directed against lymphocyte surface antigen. At low concentrations of ConA the large lymphocytes of the bursa of Fabricius adhere more rapidly than the small lymphocytes of the blood and thymus. Mouse lymph node lymphocytes adhere in the same manner as small chicken lymphocytes.     

Oxytocin and pair compatibility in adult male rhesus macaques (Macaca mulatta)

Pair housing is considered one of the best ways of promoting psychological wellbeing for caged macaques. However, incompatible partnerships can result in stress or aggression. Though previous studies have analyzed the role of variables such as age, weight, gender, and temperament on pair compatibility, few have examined the relationship between physiological parameters and pair compatibility. Oxytocin is known to promote prosocial nonsexual behavior in various primate species and may serve as an indicator of pair compatibility. In this study, we examined the association between peripheral oxytocin levels and prosocial behaviors in isosexual pairs of male rhesus macaques. We hypothesized that animals that demonstrated high levels of prosocial behaviors would have higher oxytocin levels than those showing low levels of the behavior. In addition, to elucidate the relationship between oxytocin and compatibility, we compared peripheral oxytocin between the highly affiliative animals and single‐housed males identified as having multiple unsuccessful pair attempts with multiple partners. We collected plasma oxytocin on 40 pairs of monkeys that had lived together for at least 1 month and 20 single‐housed animals. Further, we simultaneously collected behavioral data on the pairs, recording prosocial interactions (e.g., groom, play). Oxytocin varied among individuals, but was highly correlated between members of a pair (r = 0.58, p < .001). Additionally, prosocial behavior was positively correlated with plasma oxytocin (r = 0.38, p < .02). However, contrary to our expectations, oxytocin did not differ between single and highly affiliative pair‐housed animals (F_(1,38) = 0.71, p = .40). Our results suggest that oxytocin may be associated with the quality of isosexual pairs of male macaques. More work is needed to determine the nature of this relationship.     

Immunological Adjuvant Effect of a Water‐Soluble Polysaccharide,CPP, from the Roots of Codonopsis pilosula on the Immune Responses to Ovalbumin in Mice

In this study, one water‐soluble polysaccharide, CPP, was purified from the root of Codonopsis pilosula. The immunomodulatory effect and the adjuvant potential of CPP on the cellular and humoral immune response of ICR mice against ovalbumin (OVA) were investigated. CPP was shown not to be lethal in vivo for mice in doses ranging from 0.5 to 4 mg. ICR Mice were immunized subcutaneously with 0.1 mg of OVA alone or with 0.1 mg of OVA dissolved in saline‐containing aluminum hydroxide gel (Alum) (0.2 mg), QuilA (0.01 and 0.02 mg) or CPP (0.5, 1 or 2 mg) on days 1 and 15. Two weeks later (day 28), concanavalin A (ConA)‐, lipopolysaccharide (LPS)‐, and OVA‐stimulated splenocyte proliferation, and OVA‐specific serum antibodies were measured. CPP significantly enhanced the ConA‐, LPS‐, or OVA‐induced splenocyte proliferation in the OVA‐immunized mice especially at a dose of 1 mg (P<0.05 or P<0.01). The OVA‐specific IgG, IgG1, and IgG2b antibody levels in serum were also significantly enhanced by CPP compared with OVA control group (P<0.05 or P<0.01). The results suggest that CPP could be a safe efficacious adjuvant for use in vaccines against both pathogens and cancer.