Abnormal immunoregulation in remission Hodgkin disease

Peripheral blood mononuclear cells from 11 patients with remission Hodgkin disease and 20 normal controls were incubated with irradiated allogeneic lymphocytes in one-way mixed lymphocyte cultures. Simultaneously, modified assays were performed by adding supplemental irradiated PBM, T lymphocytes, or adherent cells autologous to the responders. Baseline allogeneic responsiveness of patients and controls was not different. However, significant suppression (p less than .01) was demonstrated when the cultures were supplemented with patient mononuclear cells or adherent cells, an effect not found with similar supplemental cells from controls. Conversely, T-cell supplementation of control cultures produced more than twofold increases in proliferation but significantly less augmentation in the patients' cultures (p less than .01). T-cell subset analysis in six patients showed decreased helper: suppressor cell ratios. Hodgkin disease patients have adherent suppressor cells, which persist during remission, as well as a defect in T-cell helper function.     

Abnormalities of peripheral blood T lymphocyte subsets in polymyalgia rheumatica

The T lymphocyte subsets were studied by monoclonal antibodies in the blood of eight patients with polymyalgia rheumatica. The percentages of circulating T cells (OKT3+) were lower when compared with normal controls (p less than 0.02), as were the proportions of suppressor/cytotoxic (OKT8+) T cells (p less than 0.001), whereas the proportions of helper/inducer (OKT4+) T lymphocytes were not changed. Consequently, the OKT4:OKT8 ratio was higher in patients with polymyalgia rheumatica than in controls (p less than 0.001). On the contrary, circulating B cells were not altered. The decrease in peripheral blood OKT3+ and OKT8+ lymphocyte subsets suggests that there is an impairment of cell-mediated immunity in polymyalgia rheumatica.     

Circulating lymphocyte subpopulations in Crohn's disease

Circulating lymphocytes were enumerated in 28 patients with Crohn's disease and in 12 patients with other diseases by rosetting and by immunofluorescent staining using monoclonal antibodies for T-cell surface phenotypic markers [OKT3 (mature), OKT4 (helper), and OKT8 (suppressor/cytotoxic)] or polyvalent antisera for surface immunoglobulins (B cells). Total lymphocyte counts were reduced only in those with non-steroid-treated active Crohn's disease. Circulating monocyte counts, proportions of peripheral T and B cells, and percentages and absolute numbers of mature, helper, and suppressor T-cell subclasses in Crohn's disease were not significantly different than in the controls. Helper to suppressor T-cell ratios were comparable in all subjects, varying directly with numbers of helper T cells (p less than 0.05). Individual ratios of helper to suppressor T cells did not correlate with disease activity or location, the use of steroids, serum albumin, or total lymphocyte or monocyte counts. This study provides no evidence for underlying abnormalities of circulating lymphocyte subpopulations in Crohn's disease when compared to subjects with other illnesses. The characterization of lymphocyte subclasses in affected tissues is an important area of continuing investigation.     

Studies of human lymphocytes in the newborn and the aged

Proportions and absolute numbers of T and B lymphocytes were determined among 30 newborn infants and a group of 77 elderly patients 60 to 95 years of age. Total lymphocytes in the cord blood of the newborn showed a distinct elevation in total numbers of T and B lymphocytes (p < 0.005) as compared to that in blood from normal adult controls, reflecting the relative lymphocytosis of infancy. Proportions of cord blood T lymphocytes as reflected by the sheep cell rosette technic were considerably lower than those in lymphocytes from normal adult controls, however, proportions of cord blood T lymphocytes as determined by indirect immunofluorescence were not significantly different from those in controls. Old people showed a significant reduction in total numbers of lymphocytes (p < 0.005) when compared with those in normal adult controls 18 to 51 years of age. Moreover, there was a significant increase in the relative proportions of peripheral blood B lymphocytes in the elderly although the absolute numbers of B cells did not differ from those in younger controls. A significant decrease in total numbers of T cells as measured both by sheep cell rosettes and indirect immunofluorescence was recorded among older patients (p < 0.001). In addition, there was a broad increment in the incidence of various autoantibodies (antinuclear, anti-IgG, antismooth muscle, antimitochondrial and antiparietal cell) among the old people studied. No direct correlation could be determined between relative B-cell percentage increase or T-cell decrease and the presence of various autoantibodies in individual patients. Diminution in total lymphocyte counts as well as absolute numbers of T cells in the elderly may provide the cellular basis for an increased susceptibility to neoplasia and infection.     

T-lymphocyte subpopulations in rheumatoid arthritis. II. Definition by monoclonal antibodies

Samples of peripheral blood of 27 patients with seropositive rheumatoid arthritis (RA) and 27 healthy age- and sex-matched controls were coded and studied for lymphocyte subpopulations. Monoclonal antibodies and indirect immunofluorescence were used to analyse subpopulations of purified T cells: OKT3 reacts selectively with all peripheral human T cells, OKT4 defines the helper/inducer subpopulation and OKT8 the suppressor/cytotoxic T cells. RA patients had a significantly lower relative lymphocyte count (p less than 0.001). whereas the percentage of all T cells was similar in patients and controls, RA patients had a significantly higher proportion of helper/inducer cells (62 +/- 1.3 vs. 56 +/- 1.0, p less than 0.005) and significantly decreased suppressors/cytotoxic cells (25 +/- 1.5 vs. 32 +/- 1.0; p less than 0.001). This resulted in an increased "immunoregulatory ratio" of helper to suppressor cells in RA patients (2.68 +/- 0.17) compared to their normal controls (1.83 +/- 0.10; p less than 0.001). The proportions of T cells expressing HLA-D-like antigens (defined by a monoclonal antibody to human Ia) was not different in patients and controls. These findings confirm conclusions derived from our previous study of T cell subsets defined by the expression of Fe-receptors (Tm and Tg), that in the peripheral blood of patients with RA, helper mechanisms predominate over suppressor mechanisms. This derangement of the immunoregulatory balance may have an important role in the pathogenesis of seropositive RA.     

T lymphocyte subsets in patients with newly diagnosed Type 1 (insulin-dependent) diabetes: A prospective study

T lymphocyte subsets in peripheral blood from 11 newly diagnosed Type 1 (insulin-dependent) diabetic patients were studied prospectively at three time intervals: as soon as possible after diagnosis, 3 weeks and 5 months later. Lymphocytes were marked with monoclonal OKT antibodies and examined in a fluorescence-activated cell sorter. The percentage of T lymphocytes (OKT3) did not change significantly at the three study times. The percentage of helper/inducer T cells (OKT4) was high the first week after diagnosis, but decreased at the 5-month examination (p less than 0.05). The percentage of suppressor/cytotoxic T cells (OKT8) was low at diagnosis but increased at 3 weeks (p less than 0.02) and 5 months (p less than 0.01). The ratio OKT4/OKT8 lymphocytes was 2.28 at diagnosis, decreasing to 1.77 at 3 weeks and 1.87 at 5 months, compared with 1.46 for 16 age-matched control subjects. There was no significant change in the absolute number of lymphocytes. It is concluded that the distribution of T cell subsets was abnormal at the time of diagnosis, but changed towards normal within a few weeks, after which there was no significant change at 5 months. It is as yet unknown whether the high proportion of helper/inducer T cells and/or the low percentage of suppressor/cytotoxic T cells at diagnosis favour immune reactions involved in the pathogenesis of Type 1 diabetes.     

Increased sensitivity of T cells to regulation by normal suppressor cells persists in long-term survivors with Hodgkin's disease

We have studied the function of T cells in the peripheral blood obtained from long term survivors with Hodgkin's disease in order to determine the sensitivity of those T cells to normal suppressor cell immunoregulatory mechanisms. Concanavalin A-activated suppressor cells from normal donors suppressed the proliferation of lymphocytes obtained from 11 patients (56.8 +/- 3.5 percent) and from 28 allogeneic normal control subjects (39.8 +/- 2.7 percent [p less than 0.001]). When suppressor monocytes from the normal donors were studied, the mean proliferation of lymphocytes from 19 patients was suppressed 76.3 +/- 4.8 percent whereas proliferation of lymphocytes from 26 normal donors was suppressed 46.6 +/- 4.4 percent (p less than 0.0001). There was no tendency for the increased sensitivity to suppression that was observed in either assay system to return to normal as the patients' disease free interval increased from 1.5 years to 12 years. Furthermore, long-term survivors with diffuse histiocytic lymphoma, who had been treated with comparable chemotherapy, had normal sensitivity to the suppressor monocytes (45.1 +/- 3.8 percent). In Hodgkin's disease, the persistent increased sensitivity of T cells to two different normal immunoregulatory cells suggests that the response of the T cell to regulatory signals may be an important cause of the depressed cellular immunity observed in Hodgkin's disease and a clue to the etiology of the disease.     

T lymphocyte subsets in inflammatory bowel disease: peripheral blood

Peripheral blood T lymphocytes and T lymphocyte subsets have been quantified in 28 patients with ulcerative colitis and 26 with Crohn's disease by an indirect immunofluorescence technique using monoclonal antibodies: OKT3, which detects all peripheral blood T lymphocytes; OKT4 (T cells of helper phenotype); and OKT8 (T cells of supressor-cytotoxic phenotype). Eighteen normal subjects and 16 patients with a variety of non-inflammatory gastrointestinal disorders were studied as controls. No significant differences were found between patient and control groups in the proportions of circulating T lymphocytes or their subsets. When compared with normal subjects, absolute numbers of T lymphocytes were reduced in patients with active ulcerative colitis or Crohn's disease (p less than 0.05). OKT4+ T cell numbers were reduced in ulcerative colitis, whether active (p less than 0.02) or inactive (p less than 0.05) and in active Crohn's disease (p less than 0.05) Numbers of OKT8+ T cells were reduced in active Crohn's disease (p less than 0.01). There were no differences in T lymphocyte numbers between the patient groups and the disease control subjects. The OKT4+:OKT8+ ratio in patients with inflammatory bowel disease did not differ from that in controls. No relation was found between any of the parameters studied and disease activity, site, or extent of disease, or treatment with sulphasalazine or corticosteroids. The presence of Ia-like, HLA-DR antigens on T cells was detected using a double marker immunofluorescence technique. In control subjects up to 7% of OKT3+ cells were HLA-DR+. In only three patients was the proportion of HLA-DR+ cells greater than in controls. These results indicate that the pathogenesis of ulcerative colitis or Crohn's disease does not depend upon an alteration in the proportion of circulating T lymphocytes nor upon an imbalance of T lymphocyte subsets as defined by monoclonal antibodies. The reduction in T lymphocyte numbers may result from mucosal infiltration. The findings also suggest that circulating T lymphocytes are not activated.     

Peripheral blood T lymphocyte subsets in active rheumatoid arthritis--effects of different therapies on previously untreated patients

Peripheral blood T lymphocyte subset levels were prospectively analyzed in previously untreated patients with active rheumatoid arthritis (RA) with different drug regimens. Before treatment the patient group had reduced numbers of Leu 2a+ lymphocytes compared with controls (p less than 0.001). During penicillamine and chloroquine treatment a marked reduction in absolute numbers of Leu 3a+ lymphocytes was seen (p less than 0.01), whereas treatment with nonsteroidal antiinflammatory drugs was characterized by increased absolute numbers of Leu 2a+ lymphocytes (p less than 0.02). Thus, there seems to be a predictable variation of T lymphocyte subsets in RA with certain drug regimens.     

Immunoregulatory T cells in the peripheral blood of patients with Bechterew''s syndrome.

Seventeen patients with ankylosing spondylitis (Bechterew's syndrome) were investigated. Only 3 of them had detectable autoantibodies, but the IgA and IgM concentrations in serum were increased (p less than 0.05). The patients had a moderate reduction in con-A-induced suppressor cell activity of peripheral blood lymphocytes as detected in con-A/MLC assay, compared with that of 15 controls (41.0 +/- 8.6% suppression compared with 59.4 +/- 5.2%, mean +/-SEM; 0.05 less than p less than 0.1 one-sided test). No differences were found in the percentages of T gamma cells (suppressor cells) and T mu cells (helper cells) between patients an controls. This is to our knowledge the first report of con-A-induced suppressor cell activity an T lymphocyte subpopulations in the peripheral blood of patients with ankylosing spondylitis.     

The autologous mixed lymphocyte reaction in primary biliary cirrhosis: analysis of activation and blastogenesis of autoreactive T lymphocytes

Blastogenesis of autoreactive T lymphocytes in the autologous mixed lymphocyte reaction has been shown to be decreased in patients with primary biliary cirrhosis, but the mechanisms underlying this abnormality are not known. To investigate further the abnormal autologous mixed lymphocyte reaction in primary biliary cirrhosis, we measured the activation of autoreactive helper/inducer and suppressor/cytotoxic T lymphocytes concurrently with blastogenesis in 35 patients with primary biliary cirrhosis and 18 healthy controls. Blastogenesis was diminished in autologous mixed lymphocyte reaction cultures from primary biliary cirrhosis patients compared to the control subjects (25,273 +/- 20,259 dpm vs. 36,004 +/- 14,951 dpm, p less than 0.02), but cultures from patients with primary biliary cirrhosis contained significantly increased percentages of activated helper/inducer and suppressor/cytotoxic T lymphocytes: 20.6 +/- 7.9 vs. 15.5 +/- 5.3%, p less than 0.008, and 9.8 +/- 7.8 vs. 5.4 +/- 3.0%, p less than 0.02, respectively. These findings were not related to the histologic stage of liver disease or to the serum bilirubin concentration and were not associated with abnormalities of lymphocyte subsets in fresh peripheral blood specimens. We conclude that the percentage of autoreactive T lymphocytes in autologous mixed lymphocyte reaction cultures from peripheral blood is increased in patients with primary biliary cirrhosis and diminished blastogenesis in autologous mixed lymphocyte reaction cultures is not due to the loss of autoreactive T lymphocytes from peripheral blood. Diminished blastogenesis reflects a diminished proliferative response of activated, autoreactive T lymphocytes in primary biliary cirrhosis. Possible mechanisms that may account for the paradoxical findings of decreased blastogenesis and increased activation of autoreactive T lymphocytes in primary biliary cirrhosis are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of lymphocyte subsets in patients with aplastic anaemia

Lymphocyte subsets have been measured in the blood of 28 patients with aplastic anaemia. The mean helper/inducer:suppressor/cytotoxic T lymphocyte ratio (1.24 +/- 0.74) was significantly decreased in the total population in comparison to mean ratios in a normal population (1.78 +/- 0.57) and in patients with other haematological diseases (1.82 +/- 0.92). A reversed ratio (less than or equal to 1) was present in a large proportion (53%) of aplastic patients, due both to an absolute deficiency of helper/inducer lymphocytes and an increase in suppressor/cytotoxic lymphocytes. Increased HLA-DR expression, evidence of lymphocyte activation, was present in seven of 12 patients evaluated and was confined to the suppressor/cytotoxic lymphocyte population. In the bone marrow, the percentage of lymphocytes was increased two-fold compared to normal bone marrow but the ratio of T cell subsets was not abnormal. Two of four patients evaluated after haematopoietic recovery following ATG treatment showed a return to normal of the T4/T8 ratio; in two others a low T4/T8 ratio persisted despite recovery. These results indicate that lymphocyte subset imbalance and lymphocyte activation are present in many patients with aplastic anaemia, either as a contributing factor or as a result of bone marrow failure.     

Determination of sub-populations of circulating T lymphocytes in alcoholic cirrhosis using monoclonal antibodies OKT3, 4, 5, Leu 2 and Leu 15. Effect of hepatitis B virus infection

Peripheral T lymphocyte subpopulations were quantified in 24 alcoholic cirrhotic patients, 11 of them having anti-HBs and/or anti-HBc antibodies, and were compared with 35 healthy control subjects, 10 of them having anti-HBs and/or anti-HBc antibodies. The monoclonal antibodies utilized (OKT3, OKT4, OKT8 in simple staining, Leu 2 and Leu 15 in double staining) are considered as markers of mature (CD3), helper (CD4), cytotoxic/suppressor (CD8, Leu 2), suppressor (Leu [2+ 15+), and cytotoxic (Leu 2+ 15-) T cells. In cirrhotics, when compared to controls, the number of CD3 cells was reduced (p less than 0.01); the proportion of CD4 cells was within normal range, and that of CD8 cells diminished (p less than 0.001), contrasting with an increased proportion of Leu 2+ cells (p less than 0.01), related to an increased proportion of Leu 2+ 15+ cells. Leu 2+ 15- lymphocytes were within normal range. In control subjects, a decreased proportion of Leu 2+ 15+ cells was found (p less than 0.05) when Ac HBs and/or Ac HBc were present. In cirrhotics having at least one serologic marker of hepatitis B virus infection, when compared with negative ones, increased proportions of Leu 2+ (p less than 0.05) and Leu 2+ 15+ (p less than 0.05) cells were found. These results show that data concerning T lymphocyte subpopulations are conflicting when various types of antibodies are used. However, they suggest abnormalities of immune regulation, possibly a defect of T suppressor cell function. Hepatitis B virus infection probably modifies immune regulation in alcoholic cirrhosis, and perhaps in normal subjects.     

SUBACUTE THYROIDITIS: ACTIVATED HLA-DR AND INTERFERON-γ EXPRESSING T CYTOTOXIC/SUPPRESSOR CELLS IN THYROID TISSUE AND PERIPHERAL BLOOD

Using a two-colour direct immunofluorescence staining technique, we investigated activated HLA-DR-expressing T helper and T cytotoxic/suppressor cells in peripheral blood of six patients with subacute thyroiditis at referral and at follow-up and in blood from 20 controls. In three of the patients, thyroid fine-needle aspirates were examined as well. At referral, all patients had elevated blood levels of activated T helper and T cytotoxic/suppressor cells 2 (2-4)%, median and range, vs 0 (0-2)%, P less than 0.001 and 12.5 (2-24)%, vs 0 (0-1)% P less than 0.001). At follow-up, the activated proportion of T helper cells had become normal whereas some activated T cytotoxic/suppressor cells remained, 7 (0-8)%. No significant changes in total T cell number were detected when data at referral and at follow-up were compared. In thyroid aspirates, HLA-DR expressing thyrocytes were observed; the total proportion of T cytotoxic/suppressor cells was elevated (70% compared with 35% in blood) and 70% of the T cytotoxic/suppressor cells were HLA-DR+. Furthermore, 55% of the thyroid-infiltrating lymphoid cells were positive for interferon (IFN-gamma+). The finding of activated T cytotoxic/suppressor cells in the blood and thyroid tissue in subacute thyroiditis is consistent with a viral aetiology. Furthermore, intrathyroidal IFN-gamma+ lymphocytes are likely to contribute to expression of major histocompatibility complex (MHC) class II antigens on thyrocytes. No autoantibodies, however, were detected, which suggests that aberrant expression of MHC class II molecules alone is not sufficient to provoke an autoimmune response.     

Lymphocyte subpopulations of blood and alveolar lavage in blastomycosis

Patients with blastomycosis were found to have differing lymphocyte populations depending on the extent of disease manifestations and whether or not therapy had been started. Patients with recovering pulmonary blastomycosis who had been receiving antifungal treatment for at least four weeks had lymphocyte subpopulations no different from control donors. Patients with treated extrapulmonary blastomycosis had similar T helper (TH) to T suppressor (TS) ratios compared to recovering pulmonary patients and control subjects; this ratio gives a false impression because extrapulmonary blastomycosis patients had a reduced absolute number of lymphocytes with either marker. In bronchoalveolar lavage fluid, pulmonary blastomycosis patients who were clinically improved while receiving antifungal therapy had fewer TH cells and a greater number of lymphocytes with the TS marker than did control subjects. Patients with pulmonary blastomycosis prior to therapy had a smaller TH/S ratio than the other groups in peripheral blood primarily due to a reduction in the circulating TH fraction in both absolute numbers of cells and in the percentage of total T lymphocytes. Pulmonary blastomycosis patients re-evaluated after at least four weeks of antifungal therapy had TH/S ratios that were similar to normal persons. This increase in TH lymphocytes corresponded to clinical improvement and in a temporal correlation to that described for the development of specific immunity in this illness.     

Lymphocyte phenotype and lymphokines following anti-thymocyte globulin therapy in patients with aplastic anaemia

Twenty-two patients with adult onset aplastic anaemia were analysed before and after therapy with anti-thymocyte globulin (ATG). Lymphocyte phenotype, lymphokine levels or production, and haematopoietic progenitor cell number were measured 3 months after therapy; clinical response was determined 1 year post-therapy. By flow cytometry there was a significant reduction in both the proportion and absolute number of peripheral blood lymphocytes expressing activation antigen Tac (IL-2 receptor) and in the proportion of HLA-DR+ lymphocytes. For T cells bearing HLA-DR, there were proportional decreases in both activated helper and suppressor cells. There was no statistically significant difference pre-ATG to post-ATG in the absolute numbers of total, helper and suppressor lymphocytes. In all 10 haematologic responders the number of Tac bearing lymphocytes after ATG therapy was in the normal range, but half of 12 non-responding patients continued to have abnormally elevated numbers of Tac+ T cells. The proportion of Tac+ cells were not related to transfusion history. Gamma-interferon levels in serum by radioimmunoassay were elevated in almost half the aplastic patients; post-ATG, gamma-interferon was detectable in only three patients. Haematologic response to ATG therapy was associated with increased numbers of haematopoietic progenitors post-treatment, but pre-treatment values were not predictive of a response. These results are consistent with a pathogenic role for activated T-cells and their lymphokine products and suggest that the target of ATG therapy may be a Tac+ lymphocyte.     

Lymphocyte subpopulations in sarcoidosis: correlation with disease aetivity and duration.

We studied lymphocytes from the peripheral blood of 29 sarcoid patients to relate T- and B-cell populations with disease activity and duration. In patients with acute (less than 1 year) and chronic (greater than or equal to 9 years) active disease, the absolute lymphocyte count was reduced; the absolute number of T cells was reduced; and the proliferative response of lymphocytes to phytohemagglutinin was depressed compared with control subjects. Ten of 21 patients with active disease had 5% to 32% atypical lymphocytes. The proportion of cells bearing surface immunoglobulin (Ig) was increased in patients with active disease, but the absolute number of cells bearing surface Ig did not differ significantly from controls. However, studies using overnight in-vitro culture indicated that a large fraction of these cells bound exogenous Ig. The number of cells indentified by complement receptors was significantly reduced in patients with active disease. In contrast, patients who had complete reasolution of their disease showed no significant differences from controls in either T- or B-cell populations or in the proliferative response of their lymphocytes to phytohemagglutinin.     

Heterogeneity of immunoregulatory T-cell subsets in systemic lupus erythematosus. Correlation with clinical features

Immunoregulatory T-cell subsets as defined by differentiation antigens were studied in 32 patients with systemic lupus erythematosus (SLE) and 16 healthy persons using the monoclonal antibodies OKT 3 or anti-Leu 4 (T cells), anti-Leu 2a (suppressor/cytotoxic cells) and anti-Leu 3a (helper/inducer cells). Compared with the 95 percent confidence limits in control subjects, decreases or increases of Leu 3a+ cells were observed in 23 patients, whereas abnormal percentages of Leu 2a+ cells were observed in only 10 patients (p less than 0.002). The ratio of Leu 3a+ to Leu 2a+ cells varied over a much broader range (0.31 to 4.14) in patients with SLE than in control subjects (95 percent confidence limit 1.04 to 2.20). Furthermore, the helper:suppressor ratio correlated significantly (p less than 0.001) with a numerical clinical characterization of the patients. A low helper: suppressor ratio was observed in patients with severe renal disease, thrombocytopenia and onset of SLE by 20 years of age. Patients with a high helper:suppressor ratio had multisystem disease including lymphadenopathy, but only rarely SLE renal disease. Patients with a normal helper:suppressor ratio had the most widespread multisystem disease, often involving the kidneys and the central nervous system. The ratio was not correlated with duration of illness, disease activity or corticosteroid dosage in the patients examined. The study suggests that SLE is not one disease entity, but rather a symptom complex with different immunoregulatory abnormalities and associated manifestations.     

Transfusion history, T cell subsets and natural killer cytotoxicity in patients with colorectal cancer

Blood transfusions are associated with clinical phenomena which are attributable to immune suppression. Since suppression of immune function is associated with a high risk of spontaneous malignancies, we studied T cell subsets and natural killer (NK) cytotoxicity in colorectal cancer patients and correlated the results with patients' transfusion histories. Twelve percent (14) of the 115 patients had been transfused an average of 19 years previously. Recipients of blood transfusions had low levels of peripheral lymphocytes (p = 0.191), T cells (p = 0.015), helper cells (p = 0.016) and suppressor cells (p = 0.2651) compared to previously untransfused patients. NK cytotoxicity was also significantly reduced in transfusion recipients although NK cell numbers were comparable in both groups. These results support previous studies indicating that blood transfusions cause lifelong immune modulation in the recipient. Since blood transfusions have numerous beneficial effects and immune modulation is often beneficial, longitudinal studies are necessary to define the lifetime risks and benefits.     

Helper and suppressor T-cell function in HIV-infected hemophilia patients

T-lymphocyte helper and suppressor functions were assessed in 61 hemophilia patients. Twenty one patients were HIV-negative (Group 1), 27 were HIV-positive without having AIDS-related complex (ARC)/AIDS (Group 2), and 13 had ARC/AIDS (Group 3). T, CD4-positive, or CD8- positive T lymphocytes were cocultured with B lymphocytes and pokeweed mitogen for 6 days and immunoglobulin producing cells were assessed in a reverse hemolytic plaque assay. In HIV-infected patients, T cells as well as the CD4-positive T cell subset exhibited reduced helper (P less than .01, Group 2; P less than .0005, Group 3) and elevated suppressor activity (P less than .02, Group 2; P less than .005, Group 3), whereas no significant difference was found between HIV-negative patients and controls. The number of CD4-positive cells was not correlated with CD4 cell function. CD4-positive cells showed no helper activity (less than 10% of control T cells) in 8/11 (73%), but an excessive suppressor activity (greater than 80% suppression of plaque formation) in 6/11 (55%) Group 3 patients. Our results show that defective helper and elevated suppressor functions of T cells in HIV-infected patients are caused not only by a change in the CD4/CD8 cell counts but also by functional abnormalities of the CD4-positive T-cell subset. These abnormal helper and suppressor functions may play a role in the development of the immunodeficiency state of AIDS patients.