Production of H-Y Antibody by Female Mice that Fail to Reject Male Skin

WHEN inbred mice are grafted with skin from inbred donors that differ from the recipients only by a single minor histocompatibility antigen, it is commonly observed that some recipients will retain their skin grafts while others will reject them. This is true of incompatibility for H-Y antigen, which is responsible for the rejection of male grafts by otherwise histocompatible inbred females of the same inbred strain¹. Thus in the DBA/2 (DBA) strain, male-to-female skin grafts are rejected by only some recipients; in the C57BL (B6) strain, females always reject male skin; and C3H/An (C3H) females usually accept male skin grafts indefinitely.     

Hybrid immune response to parental liver tissue grafts

Parental-to-F₁-hybrid liver tissue grafts in like-sex donor-recipient combinations survive indefinitely, although several F₁ recipients demonstrate an immunological response to the parental graft. Female F₁ recipients, particularly those carrying theH-2 ^b haplotype, respond vigorously to male parental liver grafts. However F₁ female responses to male parental liver tissue grafts differ substantively from the responses of parental females to syngeneic male grafts. C3H male liver grafts are rejected vigorously by F₁ females as long as the F₁ carries theH-2 ^b haplotype. These findings support previous reports of strong immunological responses to C3H H-Y antigen in female F₁ and C3H.SW animals, a response which is absent in C3H females. Female F₁ hybrids carrying theH-2 ^b haplotype do not reject grafts of B10 or B6 male liver as rapidly as do B10 or B6 parental females. This reduced F₁ response may be related to the formation of hybrid antigens and consequent alteration of the anti-H-Y response. Alternatively, cells that specifically suppress the anti-H-Y response may be present in F₁ hybrids. Factors responsible for suppression appear to be controlled by non-MHC antigens, at least in (OH x B6 or B10) F₁ hybrids.     

Studies on the H-Y antigen in rats

The H-Y antigen has been studied under a variety of experimental conditions in BN and Lewis rats. The results indicate that 1. graft size is crucially important in determining the fate of male skin isografts on females; 2. H-Y incompatible ear skin grafts survive significantly better than those of trunk origin; 3. prior exposure of females to male lymphoid cells greatly increases their capacity to reject male skin isografts; 4. neonatal castration has no influence on the expression of H-Y; 5. multiparity can induce unresponsiveness to H-Y; and 6. although BN females respond better than do Lewis females to H-Y, the antigen is stronger in Lewis males. These findings are compared with the results of similar experiments conducted with mice.Submitted in memory of Dr. Joy Palm, member of the Wistar Institute, who pioneered the genetic analysis of histocompatibility in rats.     

Modulation by neonatal thymectomy of the reproductive axis in male and female rats during development

The effects of neonatal thymectomy, at 3 days of age, on parameters of the reproductive axis were examined in male and female Sprague-Dawley rats. Gonadal and accessory sex tissue (male: epididymis, seminal vesicle, and ventral prostate; female: uterus) weights as well as anterior pituitary, spleen, and adrenal weights were determined in the thymectomized and sham-thymectomized animals at 20, 30, 40, 50, 60, and 90 days of age. Plasma gonadotropin concentrations as well as pituitary content of the gonadotropins and prolactin were assessed at each of these time intervals. No significant difference in gonad and accessory sex tissue weights was detected in thymectomized versus sham-operated controls at each of these times. Adrenal weights were increased in thymectomized animals compared with controls at 50 days of age and older in male rats and at 90 days in females. Spleen weights were decreased in the thymectomized males at 50 and 60 days of age. Thymectomy did not affect the spleen weight of females. Plasma concentrations of gonadotropins were unaffected in thymectomized males but were altered in females during the pre- and peripubertal period (Days 20-40). Vaginal opening, however, occurred at the same time in the thymectomized and control females. Pituitary gonadotropin and prolactin content were unaffected by thymectomy of the females, except at 90 days when pituitary luteinizing hormone (LH) content was lower in thymectomized than in control animals. LH and prolactin content were significantly reduced in the males at 60 and 90 days of age. These results demonstrate that there are sexual differences in the effects of thymectomy on parameters of the reproductive axis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Difference in B cell mitogen responsiveness between closely related strains of mice.

Spleen cells from C3H/HeJ mice respond very poorly to the mitogenic action of endotoxin (LPS) in vitro whereas cells from a very closely related strain, C3H/HeN respond very well. An analysis of the genetic similarity of these two strains was performed. There is no significant MLR measurable between cells of these strains under a variety of culture conditions. They do not manifest a significant graft-vs-host response nor do they reject reciprocal skin grafts. Because of this genetic similarity, it is possible to reconstitute the LPS response of nonresponder mice by an adoptive transfer of spleen cells from C3H/HeN mice. This strain pair should therefore prove useful in analyzing the genetic and cellular basis of endotoxin reactivity.     

A sex-limited serum protein variant in the mouse: Hormonal control of phenotypic expression

The sex-limited protein (Slp) antigen of the mouse is first detected in the serum of strain DBA/2J males at 5–6 weeks of age and reaches full adult levels by 10 weeks. This antigen is normally absent in females. Immature DBA/2J males castrated at 3 1/2 weeks of age failed to develop Slp antigen, while DBA/2J females treated with testosterone propionate starting at 3 1/2 weeks developed normal adult male levels of Slp antigen. Similar hormone-influenced effects were demonstrated in adult males and females of the same strain. Experiments indicated that testosterone does not act directly in the serum to expose Slp antigenic sites. Testosterone treatment of both males and females of strain C57BL/10JSf, which does not carry the gene for the presence of the Slp antigen, failed to stimulate the appearance of the antigen. Thus, the presence of Slp antigen in the serum is dependent on both the proper genotype and the presence of male hormone.Supported by U.S.P.H.S. Research Grant GM-15419, U.S.P.H.S. Training Grant 2T01-GM-00071 (H.C.P.), and U.S.P.H.S. Career Development Award K3-HE-24,980 (D.C.S.).     

Respective influence of extrinsic and intrinsic factors on the age-related decrease of thymic secretion.

The serum level of a circulating thymic factor (FTS) described in our laboratory diminishes in mice after adult thymectomy and with age. However, thymuses from old mice, when grafted into young adult thymectomized recipients lacking circulating FTS, can still partially restore the circulating FTS level of the recipients, whereas newborn thymuses are less efficient in restoring the serum level of FTS in old recipients than in young adult thymectomized recipients. Taken together, our results suggests that in addition to an intrinsic deficiency of the thymic secretion, "environmental" factors play a role in the disappearance of circulating FTS with age, the more so since we observed in old mouse sera factors inhibiting the in vitro biologic activity of FTS, factors that are absent from young mouse sera.     

Autoradiographic studies with 3H 1,25 (OH)2 vitamin D3 and 3H 25 (OH) vitamin D3 in rat parathyroid glands

Summary After injection of radiolabeled 1,25 (OH)₂ vitamin D₃, nuclear concentration of radioactivity is observed in parenchymal cells of the parathyroid gland in pregnant, adult male, and 10-day male neonatal rats. In competition studies with unlabeled 1,25 (OH)₂ vitamin D₃, but not with 25 (OH) vitamin D₃, nuclear uptake is prevented. Experiments with ³H 25 (OH) vitamin D₃, in contrast to ³H 1,25 (OH)₂ vitamin D₃, do not show nuclear concentration in cells of the parathyroid. The results of the autoradiographic studies suggest the presence of receptors for a direct effect of 1,25 (OH)₂ vitamin D₃ on the parathyroid gland for modulation of parathyroid hormone secretion.     

Effector and regulatory cells in autoimmune oophoritis elicited by neonatal thymectomy.

(C57BL/6 x A/J)F1 (B6AF1) mice thymectomized between days 1 and 4 of age develop autoimmune oophoritis (D3TX oophoritis) 4 to 6 wk later. Oophoritis can be adoptively transferred to young recipients, and the disease in D3TX mice is prevented by reconstitution with normal adult spleen cells. The present study was further defined the nature of the effector and suppressor cells. Contrary to an earlier report, oophoritis is transferred to syngeneic and not allogeneic recipients. The spleen cells from D3TX mice when stimulated in vitro with Con A, also transfer oophoritis to adult recipients. The effector cells are CD4+: oophoritis transfer is abrogated by CD4 antibody and not by CD8 antibody and C. Spleen cells from D3TX male mice transfer disease less efficiently than female cells, thus endogenous ovarian Ag may be required for activation of effector T cells. T cells from normal adult spleen that suppress D3TX oophoritis also appear to be of CD4+ phenotype. These cells are likely to be derived from adult thymus because adult thymocytes also suppress D3TX disease. We were unable to substantiate the earlier claim that suppressor cells in normal mice are ovarian Ag specific. Thus male and female spleen cells suppress disease with comparable efficiency, and deprivation of endogenous ovarian Ag by neonatal ovariectomy of cell donors had no observable effect on disease suppression.     

Requirement of the thymus for the recovery of anti-alloantigen helper T cells from tolerance induced by intravenous presensitization with allogeneic cells

Intravenous presensitization of C57BL/6 (B6) mice with class I H-2-disparate B6-C-H-2bm1 (bm1) whole spleen cells and class II H-2-disparate B6-C-H-2bm12 (bm12) spleen cells depleted of APC resulted in almost complete elimination of the respective anti-bm1 and anti-bm12 reactivities. However, the reduced alloreactivities as assessed by Th cell capacities (proliferative responses and IL-2 production) were recovered around 8 wk after the i.v. presensitization in euthymic B6 mice. In contrast, background levels of bm1- or bm12-specific reactivities were revealed to last more than 12 wk after the presensitization in B6 mice which had been thymectomized prior to the i.v. presensitization. Such a reduced alloreactivity was also observed in the capacity to reject bm1 or bm12 skin grafts, and prolongation of graft survival was strikingly enhanced in the thymectomized group compared to that induced in the nonthymectomized group. However, there was an important difference in such prolongation in the thymectomized hosts between bm1 and bm12 grafts; a considerable percentage (greater than 80%) of bm12 skin grafts continued to take more than 5 mo, whereas about 90% of bm1 grafts were rejected by around 5 mo along with the emergence of weak, but detectable anti-bm1 Th and cytotoxic T cell activities. These results indicate that 1) i.v. presensitization regimen is capable of eliminating in vitro and in vivo alloreactive capabilities but these alloreactivities can be recovered in euthymic hosts with T cell repopulating potential and 2) there are differential requirements of the thymus for repopulating anti-bm1 (Lyt-2+) and anti-bm12 (L3T4+) T cell activities.     

Sexual selection versus alternative causes of sexual dimorphism in teiid lizards

Summary The presence and extent of sexual dimorphisms in body form (size and shape) of adult macroteiid lizards were investigated. Males were significantly larger than females in the temperate species, Cnemidophorus tigris, and in the tropical species, Ameiva ameiva and C. ocellifer. Young adult C. tigris males grew faster than young adult females within and between reproductive seasons. Adult males of all species had larger heads than adult females of the same body size; this difference increased with body size. Moreover, male C. tigris were heavier than females of the same snout-vent length. The causes and consequences of the sexual dimorphisms were also examined. The possible causes of body size are especially numerous, and distinguishing the relative influences of the various causal selection factors on body size is problematical. Nevertheless, observational field data were used to tentatively conclude that intrasexual selection was the cause of larger body size of C. tigris males relative to females because (1) larger males won in male aggressive interactions, (2) the winning males gained access to more females by repelling competitors and by female acceptance, (3) larger males consequently had higher reproductive success, and (4) other hypothetical causes of larger male size were unsupported.     

Interspecific interactions and learning variability jointly drive geographic differences in mate preferences

Co‐occurrence of closely related species can cause behavioral interference in mating and increase hybridization risk. Theoretically, this could lead to the evolution of more species‐specific mate preferences and sexual signaling traits. Alternatively, females can learn to reject heterospecific males, to avoid male sexual interference from closely related species. Such learned mate discrimination could also affect conspecific mate preferences if females generalize from between species differences to prefer more species‐specific mating signals. Female damselflies of the banded demoiselle (Calopteryx splendens) learn to reject heterospecific males of the beautiful demoiselle (C. virgo) through direct premating interactions. These two species co‐occur in a geographic mosaic of sympatric and microallopatric populations. Whereas C. virgo males have fully melanized wings, male C. splendens wings are partly melanized. We show that C. splendens females in sympatry with C. virgo prefer smaller male wing patches in conspecific males after learning to reject heterospecific males. In contrast, allopatric C. splendens females with experimentally induced experience with C. virgo males did not discriminate against larger male wing patches. Wing patch size might indicate conspecific male quality in allopatry. Co‐occurrence with C. virgo therefore causes females to prefer conspecific male traits that are more species specific, contributing to population divergence and geographic variation in female mate preferences.     

Mortality of pregnant females in Arikara villages: osteological evidence

High infant mortality and high mortality for late adolescent and young adult females suggest that obstetrical hazards may be one explanation for differences in male and female mortality curves. This possibility is investigated in Arikara skeletal series by determining the frequency of females who died with fetal remains in utero. Two females (0.9%) were so identified. Examination of the females and the fetal remains do not provide evidence that stress of childbearing was the cause of death in these cases.     

Effect of pairing in vitro on the glutathione level of male Schistosoma mansoni

The effect of in vitro incubation on the level of the intracellular nucleophile, glutathione (GSH), in adult Schistosoma mansoni was investigated. The GSH levels of freshly collected adult male and female parasites were 8.5 +/- 2.5 and 2.7 +/- 0.7 nmol/10 worms, respectively, as determined by an enzymatic assay. Twenty-four-hour incubation of unpaired males in RPMI-1640 medium at 37 C resulted in a 1.7-fold increase (P less than 0.001) in GSH level that remained elevated for at least 7 days. The increase was dependent on exogenous L-cystine, suggesting that it was due to biosynthesis of GSH. Biosynthesis in male S. mansoni was confirmed by isolating [3H] GSH from parasites incubated in medium containing L-[3H] cystine or [3H] glycine. In contrast to unpaired males, the GSH level of paired males as well as that of unpaired or paired females did not increase after 24 hr in vitro. When males that had been incubated unpaired for 24 hr were allowed to couple in vitro with freshly collected females, their GSH level fell to that of continuously paired males. These observations provide evidence that in vitro female schistosomes can influence the physiology of the male.     

The stimulatory effect of males on the initiation but not the maintenance of ovarian cycling in cotton-top tamarins (Saguinus oedipus)

Prior studies have shown that female cotton-top tamarins usually do not ovulate while living with natal groups, and most females do not ovulate until they are paired with an unfamiliar adult male. To examine the role of unfamiliar adult males on stimulating ovarian function, four cotton-top females were studied during three conditions: females living with their natal group for six weeks, living alone but exposed to a single unfamiliar adult male located 15 cm away from the female's cage for four weeks, and living with an unfamiliar adult male for six weeks. Behavior and urinary hormonal concentrations were measured during the three conditions. Exposure to the male consisted of visual, auditory, and airborne olfactory contact. First ovulation occurred during exposure to the unfamiliar male in three of the four females indicating that direct physical or sexual contact with the male is not required for onset of ovarian cycling. The fourth female did not ovulate even during six weeks of direct contact with the unfamiliar adult male. In addition, four parous females in either family groups (3) or singly caged (1) were examined for ovarian function 4–6 months after the death or removal of their mates. All femals continued to cycle in the absence of the male indicating that the male was not needed to continue ovarian cycling. In fact, two of the females were pregnant at the time their males died and both delivered normal infants and resumed cycling. The results of this study indicate that an unfamiliar adult male may facilitate the onset of ovarian cycling without being in direct contact with the female and visual, auditory, or airborne olfactory cues may be involved. Once repeated ovarian cycling occurs the male is not required to maintain ovarian function.     

Some endocrine aspects of the thymus gland.

In studies of the mouse thymus, lymphocyte mitoses are seen to be most frequent in the thymus cortex. There is evidence from thymic grafts that a hypothetical factor, thymopoietin, may stimulate mitosis of thymic lymphocytes. It is a factor which is postulated to act in conjunction with the PAS-positive mesenchymal reticular cells and epithelial reticular cells of the cortex. The thymus medulla is necessary for the integrity of thymic grafts, and may also elaborate a secretion for maintaining the cellular functions of the gland. Thymectomy has been used as a gauge for judging normal thymic function and results, in the mouse, in lymphopenia, degeneration of spleen and lymph nodes, delayed rejection of skin allografts, reduced ability of spleen cells to mount the graft versus host reaction, and reduced primary immune response to certain antigens. Correction of these deficiencies offers a means of evaluating various thymic extracts and grafts. Lymphocytosis-stimulating hormone (LSH) is known to maintain the peripheral lymphoid organs and cause lymphocytosis in the thymectomized animal. Diffusion chamber studies of thymic grafts also show restored lymphoid tissue by a cell-free factor (CIF). These two factors may be the same and probably represent the basis of the highly purified lymphocyte-stimulating proteins, LSHr and LSHh, which restore the L/P ratio in thymectomized animals and may stimulate lymphopoiesis in spleen and lymph nodes. LSHr, unlike LSHh, increases the total lymphocyte count. LSHr has been found to increase the humoral antibody response in neonatal mice both by the PFC technique and by direct hemolysis of sheep erythrocytes. Homeostatic thymic hormone (HTH) is a thymic extract of small molecular weight and contains nucleic acid. In the thymectomized guinea pig it has been found to maintain normal levels of lymphocytes in the blood, spleen and lymph nodes, to restore antibody titers to typhoid H antigen and to restore the toxic allergic reaction. Thymic humoral factor (THF) is of smaller molecular weight (less than 1,000) and probably is not a protein. It also enhances lymphoid proliferation in neonatally thymectomized mice. There is evidence that THF participates in humoral antibody formation because it stimulates PFC formation from neonatally thymectomized mice after inoculation with sheep erythrocytes. Its effects on cell-mediated immunity are seen from findings that injection of THF restores the ability of thymectomized mice to reject skin allografts. THF enables spleen cells from thymectomized or neonatal animals to mount the graft versus host reaction, and causes maturation of bone marrow cells and spleen or lymph node cells so that they can participate in the graft versus host reaction. It has been reported to stimulate lymphocytes to kill isogeneic tumor cells in vitro. Thymosin is protein extracted from the thymus. It has been found to alleviate leukopenia slightly and provide some improvement in lymphoid histology in thymectomized mice...     

Stimulation of maternal responsiveness after pregnancy termination in rats: Effect of time of onset of behavioral testing

To assess the effects of varying the time interval between surgical pregnancy termination and onset of behavioral testing on the expression of maternal behavior, both responsiveness to foster young and nest building-were measured in rats ovariectomized (O), hysterectomized (H), ovariectomized and hysterectomized (OH), or sham-operated (I) on Day 17 of pregnancy at 10:00 and first tested for maternal responsiveness 6, 24, or 48 hr after surgery. When behavioral testing was started 6 hr after surgery O and OH groups responded maternally to foster pups faster than H or I groups, and H females responded maternally faster than I animals (O = OH < H < I). In animals first tested 24 hr after surgery shorter latencies to retrieve and group foster young and nest build were found in the three pregnancy-terminated groups than in I animals, while the three pregnancy-terminated groups did not differ from one another with respect to either behavioral measure (O = OH = H < I). In contrast, when testing was initiated 48 hr after surgery, hysterectomized (H) animals responded maternally faster than did ovariectomized (O and OH) or intact pregnant (I) groups (H < OH < I, H < O = I). These data demonstrate that varying the time of onset of behavioral testing after surgical pregnancy termination affects elicitation of responsiveness to foster young and also affects nest building behavior in pregnancy-terminated animals. The differences in onset of maternal behaviors among pregnancy-terminated animals are discussed in relation to progesterone and estrogen secretion after surgery.     

Pair bonding and "the widow effect" in female prairie voles

We conducted field and laboratory experiments with the well-studied monogamous prairie vole, Microtus ochrogaster, to distinguish among three hypotheses for the failure of females that lose their mates to bond with a new male ("the widow effect"). The reproductive value hypothesis predicts that males prefer young to older females because they potentially have a longer reproductive lifespan. The mate rejection hypothesis predicts that females will prevent repairing by aggressively deterring males that might harm their current offspring. The misdirected paternal care hypothesis assumes that females will mate during postpartum estrus and thus will be pregnant and/or nursing young throughout the breeding season; males will avoid pairing with older females to avoid providing care to unrelated offspring and/or because of a delay to the next breeding opportunity. Males associated and bred more with older than young females, allowing us to reject the reproductive value hypothesis. Our results were consistent with the male rejection hypothesis in that females were aggressive toward unfamiliar males. Our results were most consistent with the misdirected paternal care hypothesis in that once females started breeding, they continued to become pregnant and nurse young throughout the study period. Thus, our findings suggest that the potential of misdirected paternal care and delayed mating opportunity in conjunction with the aggressive behavior of females toward unfamiliar males are likely explanations for the lack of repairing for widow females.     

The development of affiliative and coercive reproductive tactics in male chimpanzees

Like many animals, adult male chimpanzees often compete for a limited number of mates. They fight other males as they strive for status that confers reproductive benefits and use aggression to coerce females to mate with them. Nevertheless, small-bodied, socially immature adolescent male chimpanzees, who cannot compete with older males for status nor intimidate females, father offspring. We investigated how they do so through a study of adolescent and young adult males at Ngogo in Kibale National Park, Uganda. Adolescent males mated with nulliparous females and reproduced primarily with these first-time mothers, who are not preferred as mating partners by older males. Two other factors, affiliation and aggression, also influenced mating success. Specifically, the strength of affiliative bonds that males formed with females and the amount of aggression males directed toward females predicted male mating success. The effect of male aggression toward females on mating success increased as males aged, especially when they directed it toward females with whom they shared affiliative bonds. These results mirror sexual coercion in humans, which occurs most often between males and females involved in close, affiliative relationships.     

The host antigen phenomenon in experimental murine schistosomiasis: The transfer of 3-week old Schistosoma mansoni between two inbred strains of mice

A surgical technique for the transfer of 3-week old Schistosoma mansoni to the mesenteric veins of mice is described. Parasites grown in a donor C3H/StCrl strain survive on transfer to recipient C57BL/10J mice despite prior immunization with C3H/StCrl cells or skin grafts. The findings indicate that the ‘species-specific’ mouse host antigens associated with adult worms in xenogeneic transfers do not have an allogeneic basis in these two strains.