Clinico-immunological study of the patients infected with Mycobacterium avium complex (MAC)]

Lymphocyte functions of the peripheral blood in the patients infected with MAC (MAC-pts) were evaluated comparatively with age-matched normal controls by using flow cytometry. The results obtained were as follows: 1) In normal controls, the number of total lymphocytes and the proportion and number of T lymphocyte subsets significantly decreased with age. The proportion of natural killer lymphocytes significantly increased in elder controls. 2) In MAC-pts, the number of total lymphocytes and T lymphocyte subsets were significantly lower and the proportion of natural killer lymphocytes were higher respectively than normal controls. 3) The lymphocyte proliferation induced by PPD-S stimulation in vitro in MAC-pts was significantly lower than the normal controls in both age groups of 50-69 and 70-89 years old. 4) The lymphocyte proliferation induced by PPD-S stimulation in MAC-pts was increased slightly by adding recombinant IL-2 and significantly higher by depletion of monocytes. By combination of both treatments, it recovered to the level of normal controls. From these results, we suggested that the decline of lymphocyte proliferation induced by PPD-S stimulation in MAC-pts was due to the decrease of IL-2 production by antigen committed lymphocytes and suppression by monocytes. 5) Lymphocyte proliferation induced by PHA stimulation in vitro was also significantly depressed in MAC-pts as compared with normal controls.     

Abnormalities of CD4+ T lymphocyte proliferative responses from patients with recently diagnosed insulin-dependent diabetes mellitus

To investigate the abnormalities of cell-mediated immunity in patients with recently diagnosed insulin-dependent diabetes mellitus (IDDM), we studied the responses of the two major T lymphocyte subsets from peripheral blood lymphocytes (PBL) to mitogen stimulation. Samples for PBL were obtained from a group of IDDM patients and from a group of normal controls. CD4+ and CD8+ T cells were isolated and were subsequently stimulated with three specific lymphocyte mitogens, namely Phytohemagglutinin (PHA), Concanavalin A (Con A) and Pokeweek mitogen (PWM). The proliferative response was measured by incorporation of radioactive thymidine in lymphocyte cultures which were stimulated by the three mitogens. The responses of CD8+ T cells from IDDM patients and from controls were not significantly different. However, CD4+ T cells from IDDM patients showed significantly depressed responses to PHA and Con A and to a much lesser extent to PWM. These data provide new information regarding the CD4+ T lymphocyte abnormalities found in patients with IDDM.     

Use of an Antiserum Specific for Human T Lymphocytes as a Diagnostic Reagent: Comparison with E Rosette Formation and Mitogenic Response to PHA

An antiserum with specificity for human T lymphocytes was evaluated as a diagnostic reagent in the clinical immunology laboratory. The antiserum was used in indirect immunofluorescence to detect T cells in blood samples from normal controls and patients with various disorders involving the immune system. The same samples were also examined using two established tests for T cells, the rosette reaction with sheep red blood cells (E rosette assay) and the proliferative response to phytohaemagglutinin (PHA). The antiserum and the rosette assay detected approximately the same numbers of T cells in controls, but the antiserum indicated T cell deficiency in several patients who appeared normal by rosetting or PHA reactivity. PHA stimulation in autologous plasma was depressed in a further group of patients who had normal T cell numbers by the other two tests. In vitro experiments with normal lymphocytes indicated that the E-rosette receptor was distinct from determinants detected by the T-cell specific antiserum. The immunofluorescence test with the anti-T serum provides an additional assay which appears to be more sensitive than the other two tests in detecting certain cases of T lymphocyte deficiency.     

Modulation of human lymphocyte proliferative response with aging.

Previously, we have demonstrated age-associated alterations in transmembrane signaling. One of the most reproducible alterations found in the immune response with aging is the decrease of lymphocyte proliferation on stimulation with various different mitogens. Here, we confirm that proliferative responses to stimulation with phytohaemagglutin (PHA), recombinant human IL-2, or anti-CD3 monoclonal antibody are all greater in the young (20-25 years) than old (60-87 years) population. We attempted to modulate the proliferative response using various agents acting at different levels of transmembrane signaling (pertussis toxin, cholera toxin, isoproterenol, PMA, Ca ionophore A23187), as well as at the level of the lymphocyte plasma membrane (methyl-beta-cyclodextrin, MBCD), or by using antioxidant vitamins (Vitamin E or C). None of these agents was able to restore effectively the proliferative response of lymphocytes from the aged to the level of young subjects. Even the combination of A23187 and PMA acting directly on calcium metabolism and protein kinase C activity was insufficient to restore the decreased mitogenic capacity of T cells from elderly subjects. Cyclodextrin, which decreases the cholesterol content of the membrane, increased the proliferative response of lymphocytes of elderly subjects, but not to the level of the young. Vitamin E had a very strong inhibitory effect on lymphocyte stimulation in both the age groups, except in combination with MBCD in T cells of the elderly, while Vitamin C had no significant modulatory effect. MAPK ERK and p38 activation was found to be decreased with aging in T cells after anti-CD3 mAb stimulation. Vitamin E but not Vitamin C strongly inhibited MAPK ERK or p38 activation. The direct activation of certain molecules or the modulation of the cholesterol content of the membrane seems to be effective immunomodulatory interventions with aging.     

Differences in T cell subsets between men and women with idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder, occurring predominantly in women. We studied by flow cytofluorimetry the T cell subsets in men and women with ITP and compared them with healthy sex-matched volunteers. In healthy controls, women were found to have higher proportions of T helper/inducer (Th/i) and lower T suppressor/cytotoxic (Ts/c) lymphocytes and consequently higher Th/i:Ts/c ratios than men. Accordingly, in clinical surveys, patients and controls should be matched for sex for proper comparisons. In patients with ITP in its active phase, an imbalance in T cell subsets was found in both sexes. The perturbation was more severe in women who had a marked decrease in number and proportion of Th/i lymphocytes and an increase in the proportion of Ts/c lymphocytes, whereas in men only, the proportion of Th/i lymphocytes was decreased. When patients with active disease were compared to those with ITP in remission, the decrease in Th/i subsets still persisted in both sexes but the Ts/c subset in women had returned to normal proportions. Therefore, the immune imbalance in ITP is more marked in women than men; imbalances in both Th/i and Ts/c are present in women while Ts/c appears not to be involved in men.     

手足口病患儿外周血T淋巴细胞亚群的临床研究

目的 研究于足口病患儿T淋巴细胞亚群的变化趋势,为临床治疗及预后评估提供依据.方法 采用流式细胞仪检测2008年5月1日至8月31日在北京地坛医院住院的346例手足口病患儿急性期的T淋巴细胞亚群,同时测定其中67例患儿恢复期的T淋巴细胞哑群;对其中99例患儿咽拭子标本进行RT-PCR以确定病原.埘不同样本行独立样本t检验、配对t检验或方差分析.结果 手足口病患儿T淋巴细胞业群均数低于相应年龄段正常参考值水平.重症患儿各年龄组中的T淋巴细胞(TL)/淋巴细胞(L)比值、＞1岁组T辅助细胞(Th)/L比值,以及1～2岁患儿的TL、Th及Th/抑制性T淋巴细胞(Ts)值低于普通病例(P＜0.05).患儿T淋巴细胞亚群随病程进展有逐渐上升趋势,普通患儿的TL/L及Th/L在恢复期增高(TL/L:56.3±8.6比61.1±9.1,t=2.56,P＜0.05;Th/L:30.2±7.2比34.9±7.9,t=2.90,P＜0.05),重症患儿除Ts/L和Th/Ts外,所有指标均在恢复期明显增高(P＜0.01);急性期重症与普通崽儿的TL为(1.738±0.976)×10~6/L比(2.696±1.946)×10~6/L(t=2.17,P＜0.05),Th/L为25.9±7.0比30.2±7.2(t=2.34,P＜0.05),Th为(0.864±0.550)×10~6/L比(1.459±0.879)×10~6/L(t=2.90,P＜0.01),L为(3.352±1.458)×10~6/L比(4.664±2.435)×10~6/L(t=2.32,P＜0.05),恢复期两组比较差异无统计学意义(P＞0.05).肠道病毒(EV)71阳性患儿T淋巴细胞亚群各值均低于阴性患儿,但差异无统计学意义(P＞0.05).结论 T淋巴细胞免疫功能可能与手足口病发病及病情发展有关.     

Immunomodulatory effects of treatment with naproxen in patients with rheumatic disease

We evaluated the effects of a nonsteroidal antiinflammatory drug, naproxen, on phytohemagglutinin (PHA)-induced lymphocyte proliferation. When added in vitro to cultures of peripheral blood mononuclear cells, naproxen enhanced the proliferative response toward PHA of lymphocytes from rheumatoid arthritis (RA) patients but not from healthy volunteers, and it reduced prostaglandin E2 (PGE2) synthesis in the cultures. Oral treatment for 7 days with naproxen also resulted in a significant enhancement of the in vitro PHA-induced proliferation of lymphocytes from RA patients and from age-matched control patients with noninflammatory rheumatic diseases, but not from young healthy controls. This enhancement of PHA-induced lymphocyte proliferation after oral intake of naproxen was not accompanied by diminished in vitro PGE2 production in the cultures. It did occur when PGE2-producing monocytes were removed and when in vitro PGE2 synthesis was blocked with indomethacin. We conclude that oral treatment with naproxen has an immunomodulatory effect and improves in vitro PHA-induced proliferation of lymphocytes from rheumatic disease patients. This effect is not due to reduced PGE2 synthesis in the in vitro cultures, but reflects a more fundamental in vivo change in immunoregulation.     

Peripheral blood lymphocyte subset distribution and function in patients with Alzheimer's disease and other dementias

Background : Until recently, new data on immune aspects of Alzheimer's disease (AD) have suggested that some facets of AD pathogenesis may be immune related. However, the effects of dementia itself on immune function have not been considered.
Aim : To compare the distribution of peripheral blood lymphocyte subsets and their function in patients with AD and other dementias.
Methods : Peripheral blood lymphocyte numbers, T cell subset distribution, proliferative responses to mitogens and suppressor cell assay were studied in a well characterised group of patients with AD, and compared to patients with other forms of dementia. Age and sex matched elderly controls were screened to exclude dementia, and young controls were medical, paramedical and laboratory staff. Analysis of variance (ANOVA) and student's t test were used for statistical analysis.
Results : The CD8 + lymphocyte population was reduced in AD and in other forms of dementia, when compared with non-demented elderly and young controls. Concanavalin A induced lymphocyte transformation was reduced in all dementia groups and in elderly compared with young controls. The changes in T cell numbers and function were not specific for Alzheimer's disease, but were found also in other forms of dementia.     

Phosphocholine-containing antigens of Brugia malayi nonspecifically suppress lymphocyte function

The immunosuppressive effect of Brugia malayi antigen (BmA) on phytohemagglutinin (PHA) driven T cell proliferation was evaluated in patients with filariasis (n = 14) and compared to control individuals (n = 12). When peripheral blood lymphocytes were co-cultured with BmA and PHA, BmA markedly suppressed the T cell proliferative response to PHA in both filarial patients and control individuals in a dose-dependent manner. The suppression resulted neither from any direct toxicity of BmA nor from nonspecific absorption of the PHA mitogenic activity by BmA. The major suppressive component appears to be phosphocholine (PC), an immunodominant molecule present in abundance on filarial parasites and on circulating filarial antigen. Both purified PC as well as PC-containing antigens affinity purified from BmA were capable of suppressing the proliferative responses of co-cultured autologous lymphocytes to PHA. The suppressive activity was not abolished by mitomycin-C treatment and was greater in patients with filariasis than in normal controls, suggesting that levels of PC-containing antigens determines the magnitude of the suppressive effect of PC-antigen. Further, as induction of the suppressive activity was completely abrogated when antigen pre-treated cells were T cell-depleted, the suppressive effect appears to be mediated primarily by T cells.     

The clinical outcome of autoimmune thrombocytopenic purpura patients is related to their T cell immunodeficiency

Summary. In this work we have furthered the understanding of the alterations of T lymphocytes from 29 patients with active autoimmune thrombocytopenic purpura (ATP) and the clinical significance of their lymphocytes. An increased percentage of in vivo activated (CD25+ and DR+) T lymphocytes was found in ATP patients with respect to that found in 22 healthy controls. The function of these T cells measured as the proliferative response to polyclonal mitogenic signals is heterogeneously impaired in ATP patients. T lymphocytes from 65·5% (19/29) of the ATP patients showed a decreased proliferative response to these mitogenic signals. This functional alteration is associated with a redistribution of the T cell compartment in these patients' peripheral blood since a significant decrease of CD4+ T lymphocytes was found.
We have also found that the impairment of the T cell function is different in the diverse clinical situations of the disease. Those with stable, untreated disease showed a marked decrease in the T cell proliferative response to mitogens. Furthermore, those patients who did not respond either to steroids or to splenectomy showed significantly reduced T lymphocyte blastogenesis after phytohaemagglutinin (PHA) stimulation in comparison to that found in responding patients.     

慢性丙型肝炎病毒感染者外周血淋巴细胞增殖反应

目的　观察慢性丙型肝炎患者外周血淋巴细胞对丙型肝炎病毒（ＨＣＶ） 抗原刺激的增殖反应．方法　外周血单个核细胞（ＰＢＭＣ） 与ＨＣＶ 抗原ｃ２２ 、ｃ３３ 、ｃ１００ － ３ 、ＮＳ５ 和植物血凝素（ＰＨＡ） 分别共同孵育,加入胸腺嘧啶核苷（３ ＨＴｄＲ） ,然后收集细胞于液闪仪测定每分钟脉冲数（ｃｐｍ） ．结果　根据对不同ＨＣＶ 抗原的淋巴细胞增殖反应发现,以ｃ２２免疫原性最强,ｃ１００ － ３ 次之：淋巴细胞激活与ＨＣＶ 基因型关系不大;健康对照和慢性乙型肝炎患者对各ＨＣＶ 抗原未能显示有效的淋巴细胞增殖反应;与健康对照比较,慢性丙型肝炎和乙型肝炎患者对ＰＨＡ 刺激的淋巴细胞增殖反应降低．结论　ＨＣＶ 抗原ｃ２２ 免疫原性最强,丙型肝炎患者对ＨＣＶ 抗原的淋巴细胞增殖反应系特异性;慢性丙型肝炎和乙型肝炎患者存在抑制的细胞免疫应答．     

Functional studies of cell-mediated immunity in haemophilia and other bleeding disorders

Defects of immunoregulation which occur in haemophilia, reflected by numerical changes in T lymphocyte subsets, have been further investigated in functional studies. Polyclonal T-cell activation by the mitogen phytohaemagglutinin (PHA) and specific stimulation by cytomegalovirus (CMV) or herpes simplex type 2 (HSV-2) in previously sensitized subjects were studied in peripheral blood lymphocyte and in T4-cell-enriched cultures. Compared with 12 controls, the responses of 11 patients (nine with haemophilia A and two with von Willebrand's disease) to PHA were significantly reduced both in unfractionated and in T4-cell-enriched peripheral blood lymphocyte cultures. Reduced responses to PHA were found in HIV (HTLV III)-seronegative as well as -seropositive patients. There were no significant differences between the response of patients' unfractionated and T4-enriched peripheral blood lymphocytes to CMV/HSV-2 recall antigen and the control subjects, although there was evident variation in the magnitude of patients' unfractionated and T4-enriched lymphocyte responses.     

Selective loss of a subset of T helper cells in active multiple sclerosis.

Patients with active multiple sclerosis (MS) have a selective loss of a subset of T helper cells (Th), detectable by two-color fluorescence-activated cell sorter analysis of peripheral blood lymphocytes. By using pairs of monoclonal antibodies to the T-cell subset markers CD4 (Th) and CD8 [T suppressor/cytotoxic cell (Ts)] and the common leukocyte markers Lp220 and Lp95-150, five phenotypically distinct T-cell subsets have been identified in peripheral blood: two CD4+ Th cell subsets and three CD8+ Ts cell subsets. The frequencies and absolute numbers of these five populations were measured in patients with active and inactive MS and were compared with those in healthy age-matched controls and in patients with other neurologic diseases. A high frequency of patients with active MS (80%) had a selective reduction of one Th subset (CD4+ Lp220+) compared with normal controls (P less than 0.001) or patients with inactive MS (P less than 0.001). Three patients examined sequentially had a further loss of the Lp220+ Th subset as disease activity progressed. The proportion of two Ts subsets was also abnormal in patients with active MS, but this defect was not restricted to that group. Total Th and Ts cell frequencies and Th/Ts ratios were not significantly different between patient and normal control groups. Thus, two-color analysis of T-cell subsets may be a more sensitive indicator than conventional single-marker assays of abnormal immune status in MS patients.     

Cellular immune response analysis of patients with leptospirosis

Peripheral blood mononuclear cells (PBMC) from acute leptospirosis patients with and without acute renal failure were studied in order to investigate the status of cellular immunity in this disease. We analyzed the lymphocyte subsets of leptospirosis patients by immunofluorescence and their responsiveness to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Additionally, we investigated the effect of the patients' sera on normal PBMC proliferative response. We observed a decrease in the CD3+ and CD4+ cell subsets in patients with and without acute renal failure, or in percentage values alone in those who had recovered from renal failure. An increase in the number of B lymphocytes was observed in all patients, compared with controls. This increase in B lymphocytes was seen even in patients who had recovered from renal failure, when the number of CD3+ and CD4+ lymphocytes had already returned to normal levels. The low PHA response observed only with lymphocytes from patients with acute renal failure suggests a suppressive effect. The proliferative response to PWM was comparable to controls, even in the patients with acute renal failure. This latter result and the expansion of the B cell number could be related to leptospiral-derived factor(s). We also showed that sera from patients with and without acute renal failure exerted some inhibitory activity on normal PBMC responses to PHA and PWM. Although the redistribution of lymphocyte subsets and the serum suppressor activity were related to acute renal failure and leptospiral factor(s), we suggest that the cellular immune system was not irreversibly affected, which is compatible with the good prognosis seen in the patients studied.     

T cell function in children with acute lymphoblastic leukaemia

Summary. Modern intensive chemotherapy has dramatically improved the prognosis of acute lymphoblastic leukaemia (ALL) in children. However, once remission has been established, quality of life and even survival may be threatened by exacerbation of viral infections in the prolonged period of continuation therapy necessary to prevent relapse. Often the viruses involved in the most severe infections are from the herpesvirus and paramyxovirus groups, suggesting that patients suffer from a defect in the cellular immunity thought essential to control such cell-associated infections. This may result from a T cell defect and, in this study, T cell responsiveness of patients under therapy for leukaemia has been investigated.
In vitro proliferative responses of peripheral blood leucocytes (PBL) to the T cell mitogen phytohaemagglutinin (PHA) were impaired in children with ALL before treatment and in the induction of remission. Impairment was attributable to reduced T cell numbers, the presence of inhibitors in the patient's serum and direct damage to lymphocytes. On achieving remission, proliferative responses to PHA of both CD4+ and CD8+ T cell subsets quickly returned to normal levels with the switch to continuation chemotherapy. Proliferative responses to Herpes simplex virus antigens were also apparently normal in the majority of patients tested in remission.
Further investigations, however, have suggested a persisting defect in CD8+ lymphocyte function. Gamma interferon secretion by PHA-stimulated PBLs was severely reduced for children with ALL in remission when compared with control children of similar age. Further, cytotoxic T lymphocyte responses to allogeneic cells could only be induced in PBL isolated from two of 13 children in remission from ALL whilst all control children of similar age and adults produced anti-allogenetic responses.     

Effect of growth hormone on immune function in normal and hypophysectomised rats]

The effect of growth hormone (GH) on immune function was studied using normal and hypophysectomised male Wistar rats. Hypophysectomy was performed by the auditory approach at 4 weeks of age. Normal and hypophysectomised rats were treated with saline or 0.4IU/body GH daily during 7 to 11 weeks of age. Histological features of the thymus and spleen and immunological parameters including blood cell counts, lymphocyte subsets, serum immunoglobulin levels, splenic natural killer activity, and mitogen-induced splenic lymphocyte proliferation were examined in the rats at 11 weeks of age. In hypophysectomised rats, the counts of peripheral white blood cells (5,513 +/- 813/microliters), lymphocytes (4,838 +/- 737/microliters), Th/i cells (2,237 +/- 329/microliters), and B cells (1,400 +/- 509/microliters), Th/i/Ts/c ratio (1.78 +/- 0.27), splenic T cell subsets (pan T: 51.0 +/- 4.3%, Th/i: 31.6 +/- 3.0%, Ts/c: 23.9 +/- 2.7%), and serum IgG level (2,148 +/- 470mg/l) were significantly decreased as compared with normal rats. Natural killer activity (17.8 +/- 4.6%) and mitogen-induced proliferation of T cells (Con A: 47.1 +/- 15.7, PHA: 51.6 +/- 12.5) were also suppressed. Hypoplasia of the thymus and spleen was observed in parallel to retarded growth of the rats. In contrast, GH supplement to the hypophysectomised rats resulted in increases in growth and lymphoid tissue, and the restoration of the counts of peripheral white blood cells (6,850 +/- 840/microliters), lymphocytes (6,211 +/- 731/microliters), Th/i cells (2,909 +/- 304/microliters), and B cells (1,947 +/- 402/microliters), Th/i/Ts/c ratio (2.04 +/- 0.34), serum IgG level (3,414 +/- 1,326mg/l), and natural killer activity (25.7 +/- 4.7%). However, splenic lymphocyte subsets and mitogen-induced proliferation of T cells were not recovered by GH treatment for 4 weeks. GH administered to normal rats increased serum IgG level (4,982 +/- 1,496mg/l) but did not affect other immunological parameters. These results indicate that humoral and cell-mediated immune function are impaired in hypophysectomised rats, but GH supplement administered to them restored most of the impaired immune function, suggesting that GH plays an important role in the development of immune function.     

Elderly high NK responders are characterized by intensive proliferative response to PHA and Con A and optimal health status

In this paper we verify a hypothesis emerging from recent immunogerontological studies assuming that an elevated level of NK activity in the elderly may be regarded as a factor compensating for a decreased reactivity of T cells. According to this assumption a high NK activity should be associated with a poor reactivity of T cells. In our study the mitogenic responses of lymphocytes of the elderly and the young high and low NK responders to phytohemagglutinin (PHA) and Concanavalin A (Con A) were measured. A high level of NK activity was not found, as would be expected from the hypothesis, to be associated with a poor reactivity to PHA and Con A. In contrast, the mitogenic response to PHA and Con A was intensive in both the young and old high NK responders while weak proliferative responses to T cell mitogens were characteristic of the young and old low NK responders. Thus, our results do not support the assumption of an association between a high NK activity and a low proliferative response to T cell mitogens in the elderly. We also found that both the elderly and the young high NK responders were characterized by an optimal health status.     

Effect of Treatment on T-Cell Function in Chronic Lymphocytic Leukaemia

T-cell functions were studied in vitro on enriched T-lymphocyte populations obtained from three groups of patients with chronic lymphocytic leukaemia (CLL): (a) untreated, (b) treated with chlorambucil, and (c) treated with chlorambucil and prednisone. The results were compared to age-matched controls and patients without CLL on comparable doses of prednisone. T cells obtained from untreated and chlorambucil-treated patients showed significantly decreased responses to phytohaemagglutinin (PHA) at short-term cultures (4 d) and in the mixed lymphocyte response (MLR). The lymphocyte responses to PHA, after 8 d in culture, were not significantly decreased. T cells obtained from CLL patients treated with chlorambucil and prednisone showed markedly reduced responses to MLR and to PHA at both time intervals. These responses were significantly less than those of cells obtained in the same manner from untreated or chlorambucil-treated patients with CLL or from patients with bronchial asthma treated with equivalent doses of prednisone. These results suggest that T cells from patients with CLL are particularly susceptible to inhibitory effects of corticosteroids. An increased susceptibility to infection has been reported in patients with CLL treated with chlorambucil and prednisone. The marked suppression of lymphocyte responses to PHA and in MLR demonstrated in this group of patients may play a role in increasing susceptibility to infections.     

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.     

Occurrence of two distinct subpopulations of suppressor cells in rats bearing chemically induced tumors

Spleen cells from rats bearing syngeneic methylcholanthrene-induced sarcomas showed impaired proliferative responses to phytohemagglutinin (PHA) as well as to the KCl tumor extract. Studies were then performed to define suppressor cell systems possibly operating in tumor-bearing rats. For this purpose, thymus and spleen cells from tumor-bearing rats were admixed with tumor-immune or normal rat spleen cells and were assayed for their suppressing activity on proliferative responses of immune spleen cells to the tumor antigens and on those of normal spleen cells to PHA. Anti-rat T cell serum and glass-adherent technique were utilized to characterize the cellular source of suppressor activity in the thymuses and spleens of tumor-bearing rats. The results indicate that there are two distinct subpopulations of suppressor cells in tumor-bearing rats. The first is glass-adherent non-T suppressor cells that inhibit lymphocyte proliferative responses both to the tumor antigens and to PHA. The second is suppressor T cells and can only impair proliferative responses of tumor-immune lymphocytes to the tumor antigens. The former cells were found in tumor-bearers' spleens, while the latter cells were present in their thymuses and spleens. It is suggested from these data that complex mechanisms of immunosuppression are working in tumor-bearing hosts, one of which can be attributed to the existing suppressor cells in those host lymphoid tissues.