Factors affecting pretreatment immune competence in cancer patients

Summary The assessment of changes in immune competence due to cancer demands carefully controlled studies with simultaneous consideration of other factors such as age, sex, and general ill health. To determine the effect of each factor, immune competence was measured in 112 healthy individuals, 134 patients with benign disease, and 350 patients with cancer (breast, colorectal, and stomach) with a wide spectrum of parameters.In normal subjects, advancing age was associated with a significant reduction in percentage lymphocyte count (LC), absolute and percentage T cell counts, and responses to phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). In patients with benign disease, advancing age was associated with depression of serum IgM levels, absolute and percentage LC, responses to PHA, and delayed cutaneous hypersensitivity (DCH) responses to tuberculin PPD (Mantoux), and dinitrochlorobenzene (DNCB), but elevation of serum IgA levels.No significant sex effects were demonstrated in either group of subjects.The effects of general ill health were determined by comparing individuals in good health (normal subjects and patients with minor benign breast disease) with those who had poor health (patients with significant benign gastrointestinal disease). The latter showed significant depression of DNCB sensitivity and lymphocyte reactivity to PHA, whereas total WBC and LC were significantly elevated.To determine the effects due to cancer, controls were matched for their general state of health and site of disease, in addition to completing all studies prior to any form of therapy. Age differences were corrected for by application of the findings of the above study. This age correction resulted in marked alterations in the significance of observed differences between cancer patients and controls. The previous significance of many differences either disappeared or was reduced, although in two instances significance was attained only after age correction. The only consistent immunodepression observed in the three types of cancer patient tested was impaired reactivity to DNCB. Responses were impaired even in early disease at all three sites.We have shown that the immunodepression exhibited by cancer patients is a summation of the effects due to age, general ill health, and malignancy. Some of the changes previously ascribed to cancer are due to these other factors.     

Clinical utility of hyperglycosylated hCG in serum taken before hydatidiform mole evacuation to predict persistent trophoblastic disease

OBJECTIVE: Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Studies on hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen, ITA) in PTD are limited. In serum samples taken before evacuation of molar pregnancies we measured the concentrations of free hCG beta-subunit (free hCGbeta), "total" hCG (hCG+hCGbeta) and ITA, and determined whether ITA, the two other hCG analytes, or the calculated ratios of hCGbeta/hCG+hCGbeta, hCGbeta/ITA and hCG+hCGbeta/ITA could predict the later development of PTD. DESIGN: A retrospective study based on blood specimens collected in the Dutch Central Registry for Hydatidiform Moles. The study group comprised 97 patients with hydatidiform moles who did not develop PTD after mole evacuation and 33 patients who did develop PTD. Methods: Serum samples from 130 patients with hydatidiform mole with or without PTD were assayed using specific (radio)immunoassays for free hCGbeta, total hCG, and ITA. From these analytes we also calculated the ratios hCGbeta/hCG+hCGbeta, hCGbeta/ITA, and hCG+hCGbeta/ITA. To predict the development of PTD from these analytes and parameters we performed receiver-operating characteristic (ROC) curve analysis, resulting in areas under the curve (AUCs) that represented the diagnostic accuracy which was rated in a range from excellent (AUC >0.9 or <0.1) to poor (AUC 0.4-0.6). Results: The diagnostic accuracy of ITA was moderate (0.618) and not different from that of free hCGbeta (0.610) and hCG+hCGbeta (0.622). CONCLUSIONS: ITA as well as the other analytes and parameters in serum taken prior to evacuation from patients with molar pregnancies cannot be used to predict the subsequent development of persistent trophoblastic disease.     

A controlled trial of Bestatin in hydatidiform mole

Summary A prospective randomized controlled trial was conducted to study whether Bestatin, an immunomodifier, can reduce the incidence of persistent gestational trophoblastic disease in patients with hydatidiform mole. A group of 21 patients (Bestatin group) received 30 mg Bestatin daily after evacuation of the hydatidiform mole. A second group of 23 patients (control group) did not receive any drug. Blood was taken for white cell counts, differential counts, lymphocyte subset counts (CD2⁺, CD4⁺, CD8⁺ and B cells) and natural killer cell activity before evacuation of the hydatidiform moles. The tests were repeated every 4 weeks after evacuation until the serum subunit of human chorionic gonadotropin (hCG) had returned to normal or until the patient had to receive chemotherapy because of persistent gestational trophoblastic disease. There was no significant difference in the age of the patients, the pre-evacuation serum hCG, or the gestational age between the two groups. Chemotherapy was needed by 6 patients in the Bestatin group (28.6%) and 3 patients in the control group (13%) because of persistent gestational trophoblastic disease. There was no significant difference in any of the immunological parameters between the two groups before or after evacuation. We conclude that Bestatin at this dosage does not improve the immunological functions or clinical outcome in patients with hydatidiform mole.     

Inhibin: a new circulating marker of hydatidiform mole?

OBJECTIVE--To define the concentrations of inhibin in serum and tissue of patients with hydatidiform mole and assess their value as a clinical marker of the condition. DESIGN--Prospective study of new patients with hydatidiform mole, comparison of paired observations, and case-control analysis. SETTING--A university hospital, two large public hospitals, and a private women''s clinic in Japan. PATIENTS--Seven consecutive referred patients seen over four months with newly diagnosed complete hydatidiform mole, including one in whom the mole was accompanied by viable twin fetuses (case excluded from statistical analysis because of unique clinical features). All patients followed up for six months after evacuation of molar tissue. END POINT--Correlation of serum inhibin concentrations with trophoblastic disease. MEASUREMENTS AND MAIN RESULTS--Serum concentrations of inhibin, human chorionic gonadotrophin, and follicle stimulating hormone were compared before and seven to 10 days after evacuation of the mole. Before evacuation the serum inhibin concentrations (median 8.3 U/ml; 95% confidence interval 2.4 to 34.5) were significantly greater than in 21 normal women at the same stage of pregnancy (2.8 U/ml; 2.1 to 3.6), and inhibin in molar tissue was also present in high concentrations (578 U/ml cytosol; 158 to 1162). Seven to 10 days after evacuation inhibin concentrations in serum samples from the same patients declined significantly to values (0.4 U/ml; 0.1 to 1.4) similar to those seen in the follicular phase of normal menstrual cycles. None of the four patients whose serum inhibin concentrations were 0.4 U/ml or less after evacuation developed persistent trophoblastic disease. Though serum human chorionic gonadotrophin concentrations declined after evacuation (6.6 x 10(3) IU/l; 0.8 x 10(3) to 32.6 x 10(3], they remained far higher than in non-pregnant women. Serum follicle stimulating hormone concentrations remained suppressed. CONCLUSIONS--In this small study serum inhibin concentrations higher than those found in the early follicular phase one to two weeks after evacuation of a hydatidiform mole seemed to be specific for persistent trophoblastic disease. Further data are needed to confirm these promising results.     

Inhibition of rosette formation by antithymocyte globulin

Summary The peripheral blood leukocytes from 29 patients with adenocarcinoma of the colon were studied sequentially for the T-cell level, the rosette-inhibition titer of antithymocyte globulin and the blastogenic response to PHA and Con A to evaluate the T-cell immunocompetence. The level of E-rosette-forming cells and the blastogenic response did not reflect the immunocompetence of the T-cell population. Fluctuations in the rosette-inhibition titer of antithymocyte globulin (ATG) were observed; an increased ATG titer indicated an unfavorable clinical course, while a decreased ATG titer was observed with patients who had a favorable clinical course. The rosette-inhibition titer with antithymocyte globulin was observed to be an important indicator of competent T cells in patients with colorectal cancer.Supported by the Physicians' Medical Education and Research Foundation and General Research Supports FundsAbbreviations used that are not spelled out in the text are: AET 2-aminoethylisothiouronium bromide; ATG Antithymocyte globulin; ALG Antilymphocyte globulin; E-RFC Erythrocyte rosette-forming cells; PHA Phytohemagglutinin; Con A Concanavalin A; E Sheep erythrocyte     

The clinical evaluation of the simultaneous measurements of human chorionic gonadotropin (hCG) and its alpha-subunit in sera of patients with trophoblastic diseases

The concentrations of human chorionic gonadotropin (hCG) and its free immunoreactive alpha-subunit (hCG-alpha) in the sera of patients with trophoblastic diseases were measured by hCG and hCG-alpha radioimmunoassay (RIA), respectively. In the sera of 12 women with hydatidiform mole large amounts of hCG and considerably high level of hCG-alpha were detected in all cases. After the evacuation of mole the serum level of these glycoproteins decreased, the leve of hCG-alpha declined more rapidly than hcg. in the sera of patients with destructive mole the concentration of hCG-alpha was usually lower than that of hCG. After hysterectomy and chemotherapy the levels of hCG-alpha declined practically paralleling that of hCG. However, when hCG had decreased to undetectable level, hCG-alpha could no longer be detected in all cases. Although in the serum of patient with choriocarcinoma involving the uterus and lungs the concentration of hCG-alpha was almost as high as that of hCG, the secretory pattern of hCG and hCG-alpha might not be closely related. The changes in the serum level of free hCG-alpha as well as that of hCG parelled the clinical course of the patients examined in this study. The present results suggest that measurements of the serum free hCG-alpha may be a useful parameter to follow the clinical course and to evaluate the efficacy of treatments of trophoblastic diseases.     

Serum relaxin in patients with invasive mole, choriocarcinoma and persistent trophoblastic disease

Human chorionic gonadotropin (hCG) is considered to be one of the factors which regulate relaxin secretion in humans. Serum immunoreactive relaxin levels are increased and are detectable by radioimmunoassay both in normal and molar pregnancy. Circulating hCG levels are increased in trophoblastic disease. In the present study, relaxin and hCG levels were sequentially measured in patients with invasive mole, choriocarcinoma and persistent trophoblastic disease. Serum relaxin levels were detectable by radioimmunoassay in these patients before treatment, though they were significantly lower than in normal pregnancy. The corpus luteum of pregnancy is the main source of circulating relaxin in normal pregnancy. The existence of a corpus luteum was confirmed in the 2 patients who underwent laparotomy. Consequently, the corpus luteum may also be the main source of circulating relaxin in trophoblastic disease. Parallel changes in hCG and relaxin levels were observed during the courses of trophoblastic disease. The finding suggests that relaxin secretion is dependent on hCG stimulation in trophoblastic disease in the presence of corpus luteum.     

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.     

Inhibition of normal allogeneic lymphocyte mitogenesis by a factor released from human tumor cells in culture

Summary Human tumor and normal cell lines in culture were examined for the release of factors capable of inhibiting lymphocyte blastogenesis. Supernatants from tumor cell cultures of melanoma, carcinoma (lung, colon, breast), sarcoma, and normal fibroblasts inhibited normal lymphocyte response to PHA. Only supernatants from the tumor cell lines C1 (colon carcinoma), 734B (breast carcinoma), and 231 (breast carcinoma) were found to inhibit both PHA and ConA responses significantly. The two breast carcinoma cell lines, 734B and 231, which also were capable of inhibiting lymphocyte responses to PPD and alloantigens, were investigated further. The inhibition of lymphocyte blastogenesis caused by the supernatant of these two cell lines could not be overcome by the addition of added mitogen. Further experiments showed that the inhibition was not due to nutrient deficiencies and the supernatants were not directly toxic to the lymphocyte cultures as judged by trypan blue exclusion.     

Characterization of guinea pig mitogenic factors. I. Evidence that antigen-induced mitogenic factor and mitogenic factor from mixed leukocyte cultures are distinct molecular entities.

Mitogenic factor from BCG-sensitized cells stimulated with antigen (PPD) was found to have a m.w. between 20 and 25,000 daltons and an isoelectric point of about 7.5. The blastogenic activity of this factor was not affected by L-fucose or heating at 56 degrees C for up to 1 hr. Mitogenic factor obtained from supernatants of allogeneic cell mixtures (MLC-MF) on the other hand, had a m.w. at 15 to 18,000 daltons and an isoelectric point of 6.5. The blastogenic activity of MLC-MF was inhibited by 0.1 M L-fucose. The factor was stable at 56 degrees C for 1 hr. An antibody prepared against MLC-MF inhibited the MLC reaction as well as the activity of MLC-MF on non-committed cells. This antibody, however, did not affect the response of lymphocytes to PHA or PPD and had no suppressive effect on PPD-MF. The antibody was not cytotoxic and its suppressive activity in the MLC response could not be absorbed out by lymphoid cells indicating that it is probably directed against a lymphocyte activation product (MLC-MF) rather than membrane antigens. The chemical and immunologic differences exhibited by PPD-MF and MLC-MF indicate that these two lymphokines are distinct molecular entities.     

Molecular basis of gestational trophoblastic diseases

Gestational trophoblastic disease (GTD) encompasses a diverse group of lesions with specific pathogenesis, morphological characteristics and clinical features. The modified World Health Organization-classification of GTD includes complete and partial hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumor, epithelioid trophoblastic tumor, exaggerated placental site, and placental site nodule. The various forms of gestational trophoblastic disease can be defined and related to discrete pathologic aberrations occurring at different stages of trophoblastic differentiation. Some of these lesions are true neoplasms, whereas others represent abnormally formed placentas with a predisposition for neoplastic transformation of the trophoblast. Except hydatidiform moles in which the cytogenetic studies have been extensively reported, the pathogenesis of other trophoblastic lesions is poorly understood. Recent studies have shed light on the molecular mechanisms of trophoblastic function, especially as it relates to trophoblastic disease. This review will focus on these advances with special emphasis on the pathogenesis of each specific form of GTD. In addition, the morphology and clinical behavior of each of these entities will be briefly discussed.     

Modulation of phytohemagglutinin-mediated lymphocyte stimulation by egg lecithin

Egg lecithin at 200 μg/ml or greater was found to abrogate blastogenic responses of human leukocyte cultures stimulated with phytohemagglutinin (PHA), concanavalin A (ConA), purified protein derivatives of tuberculin (PPD), candidin or streptokinase and streptodornase (SKSD) while leukocyte aggregation mediated by PHA, however, occurred irrespective of the presence of the lipid. Inhibition of PHA-mediated responses occurred when the lecithin was added simultaneously with the mitogen but the extent of inhibition decreased with delay in the addition of the lipid. When added 48 h after their exposure to PHA, the presence of lecithin did not change the pattern of [³H]TdR incorporation. Prior sonic treatment of an aqueous suspension of lecithin was found to render the lipid more effective in arresting lymphocyte responses than the unsonicated control. In entity, these results indicated that the lipid did not affect the viability of the leukocyte cultures nor did it seem that the lipid may interfere with the binding of the mitogen per se. It was concluded therefore, that inhibition by lecithin may most likely occur early at a time following binding of the mitogen but before the cells are committed to cellular division and it seems that the plasma membrane might be a likely site of action of the lipid.     

Reversible dysfunction of T-lymphocytes in common variable immunodeficiency.

A 30-year-old man with recurrent sinopulmonary infections, eventually fatal, was found to have common variable immunodeficiency. In addition to low serum immunoglobulin concentrations he also had lymphopenia and cell-mediated immunodeficiency as shown by cutaneous anergy and a poor lymphocyte response to phytohemagglutinin (PHA) in vitro. However, intradermal injection of PHA produced a vigorous cutaneous response, showing that some cell-mediated responsiveness remained. The responsiveness of his lymphocytes to PHA was restored towards normal (confirmed by chromosome studies) by the addition of a small number of normal leukocytes to cultures; thus a reversible functional defect in his T-lymphocytes was revealed. Experiments indicated that the defect was cellular and not due to serum factors and it was concluded that normal leukocytes restored a missing factor to the patient''s T-lymphocytes. Although counts of macrophage precursor cells in the bloodstream were low, thus contributing to the immunodeficiency, this could not have caused the reduced PHA response. Several relatives of this patient had lymphoma; two cousins had common variable immunodeficiency.     

Inhibition of mitogen and specific antigen-induced human lymphocyte proliferation by cadmium

Cadmium chloride (CdCl2) added to human lymphocyte culture inhibits the proliferative response induced by phytohaemagglutinin (PHA), pokeweed mitogen and allogenic lymphocytes in mixed lymphocyte reaction. Minimally effective concentrations of CdCl2 were 3.3, 1.6 and 1.6 microM, respectively. The inhibition was greatest when CdCl2 was added at initiation of cultures and declined if the addition of CdCl2 was postponed. The presence of CdCl2, regardless of the presence of PHA during the first 24 h of incubation suppressed the proliferative response to subsequent stimulation with PHA, indicating that cadmium affects an early step of blastogenic transformation.     

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.     

Membrane-bound/soluble IL-2 receptor (IL-2R) and levels of IL-1α, IL-2, and IL-6 in the serum and in the PBMC culture supernatants from 17 patients with hematological malignancies

The present study investigated the peripheral blood mononuclear cells (PBMC) blastic responses to PHA, PHA plus recombinant IL-2 (rIL-2) and rIL-2 alone; the expression of membrane-bound IL-2R on PHA-stimulated PBMC; and the levels of IL-1α, IL-2, IL-6, and sIL-2R in serum and in culture supernatants from PHA-stimulated PBMC in 17 patients with hematological malignancies (mean age 58.5 yr, range 22–82): 6 with non-Hodgkin’s lymphoma (NHL), 4 with Hodgkin’s lymphoma (HL), 5 with Hairy cell leukemia, 1 with chronic myelogenous leukemia, and 1 with chronic lymphocytic leukemia. The patients with HL and NHL with active disease (AD) were separated from those in clinical remission. The patients with AD were studied at diagnosis (obviously before therapy) and the patients in clinical remission were out of therapy since at least 6 mo. The lymphocyte blastogenic response to PHA was significantly lower in patients with HL and NHL with AD than in the control group. The response to rIL-2 alone was in the same range in the control group and in HL and NHL AD patients. By adding rIL-2 to PHA there was an increase of the blastogenic response of the same patients. The percentage of CD25 expressed on PHA-stimulated lymphocytes from patients with HL and NHL AD and from normal subjects is in the same range. Serum levels of IL-2, IL-6, and sIL-2R were significantly higher in HL and NHL AD patients than in controls as well as in all other hematological malignancies. Supernatants derived from PHA-stimulated PBMC were assessed for the presence of cytokines and sIL-2R by ELISA. The levels of IL-2, IL-6, and sIL-2R were significantly lower in HL and NHL AD patients than in controls as well as in all other hematological malignancies.     

In vivo and in vitro evaluation of cell-mediated immunity in patients with paracoccidioidomycosis

The cellular immune response to specific and nonspecific agents was investigated. both in vivo and in vitro, in 19 patients with paracoceidioidomycosis. In addition, the immunologic study of an investigator aceidentally inoculated with P. brasiliensis was included in this study. Nearly half of the patients showed depressed cell-mediated immune responses, as evaluated by intradermal tests with an antigenic preparation from P. brasiliensis (P.b.Ag.), ubiquitous antigens, and by the ability to develop sensitization to 2,4-dinitrochlorobenzene. A similar proportion of impaired responses was observed when the patients' lymphocytes were cultured with phytohemagglutinin (PHA). C'. albicans antigen and P.h.Ag. A factor was detected in the plasma of some patients which reduced the ability of patients' and normal lymphocytes to undergo blastic transformation. A positive correlation was found between the ability to develop delayed cutaneous hypersensitivity reactions to P.b.Ag. and other ubiquitous antigens, normal in vitro responsiveness to PHA and the absence of humoral blastogenic inhibitory factor. The inhibition of leukocyte migration, but not lymphocyte transformation, correlated positively with delayed hypersensitivity. The percentage of T lymphocytes was significantly reduced in the group of patients, being the absolute number and percentage of B cells bearing receptors tor complement normal. Two polar immunological patterns emerged. One characterized by positiveness in the skin test to P.b.Ag. and lack of significant abnormalities in cellular immunity, and another anergic to P.b.Ag., with cell mediated immunity severely depressed. Between the two polar groups, there were patients with intermediary patterns of immune response. This paper also includes the results obtained with the administration of transfer factor and levamisole to some of the patients.     

Effects of zinc on cell-mediated immunity in chronic hemodialysis patients

Thirteen healthy subjects and 20 hemodialysis patients were studied to observe the delayed hypersensitivity skin tests (DHSTs) and phytohemagglutinin (PHA)-stimulating lymphocyte blastogenesis. Significant differences were observed between the groups. Controls had a higher proportion of positive skin reaction than hemodialysis patients in relation to Escherichia coli (p<0.01) and tuberculin (PPD) (p<0.05). Regarding lymphocyte blastogenesis stimulated by phytohemagglutinin (PHA), cell proliferation was more accentuated in controls than hemodialysis patients (p<0.05). On the other hand, serum zinc was elevated in controls (78 +/- 8 microg/dL) in comparison to hemodialysis patients (71 +/- 33 microg/dL) (p<0.05). Of the 20 hemodialysis patients, 8 patients were maintained on long-term hemodialysis before and after zinc therapy, with the aim of studying DHST and PHA-stimulating lymphocyte blastogenesis. There was a significant improvement of DHST response to E. coli antigen after 100 d of zinc treatment (p<0.01), and with the discontinuation of therapy, the DHST responses decreased back to the initial values (p<0.05). Zinc administration also increased the lymphocyte proliferation induced by PHA from 31386 +/- 3974 to 42480 +/- 5242 cpm (mean +/- SD) (p<0.05). These results indicated that zinc therapy improved in vivo and in vitro DHST and lymphocyte function of hemodialysis patients and that its discontinuation suppressed all of the benefits observed.     

Cell-mediated immune responses in human infection with Onchocerca volvulus

Mechanisms involved in modulation of the immune response in persons with chronic Onchocerca volvulus infection are poorly understood. In this study in vitro reactivity of PBMC to O. volvulus antigen (Ovag), streptolysin O (SL-O) and the mitogen PHA was tested in 62 infected individuals (INF), 17 persons living in the endemic area with exposure to the infection, but with no detectable infection (END), and 7 healthy controls (CTRL) in Liberia, West Africa. Mean blastogenic responses to Ovag were minimal and did not differ between the groups. There was, however, heterogenous reactivity to Ovag in the INF and END. For example, individuals with a history of therapy, and half of those less than 17 yr old who were tested, showed high responses. No significant differences in the response to SL-O or PHA were detected between the groups. IL-2 production in response to Ovag was minimal in the majority of infected subjects. Exogenous IL-2 was found to cause a significant increase in mean responses to Ovag and SL-O in INF and END only. Similarly, Ovag did not stimulate IL-1 production in most INF, whereas stimulation with LPS led to significantly greater production of IL-1. Depletion of plastic and nylon wool adherent cells did not increase responses to parasite-related antigen in INF, END or CTRL; however, responses to SL-O were augmented in INF, an effect that was also observed in CTRL. Finally, depletion of CD8 or CD16 cells in INF by C lysis did not increase blastogenic responses. These results indicate that cell-mediated immunity to parasite-related Ag as reflected in lymphocyte responses in vitro is diminished in infected individuals, and that this may be caused by defects in T cell activation.