Phenotypic and functional analysis of cellular cytotoxicity after splenectomy

Phenotypic and functional aspects of cellular cytotoxicity were investigated in patients after splenectomy. While assays testing for natural killer cell (NK) activity and antibody-dependent cellular cytotoxicity showed a significantly reduced (p less than 0.005 and p less than 0.025, respectively) activity of the relevant cell populations, lectin-dependent cellular cytotoxicity was either normal or, in one dilution of phytohemagglutinin, even significantly increased (p less than 0.025), as compared to healthy control persons. In a search for a possible explanation for this phenomenon, it was found that the total lymphocyte count was significantly increased (p less than 0.01) in patients after splenectomy, when compared with healthy control individuals. However, neither the absolute cell count nor the percentage of Leu7+ lymphocytes showed significant differences between splenectomized patients and controls. In contrast, the percentages of (Leu7+Leu2)+, OKT11+, OKT4+ and Leu2a+ lymphocytes were significantly decreased (p less than 0.0025, p less than 0.01 and p less than 0.005, respectively) in splenectomized patients with not only the percentage, but also the absolute number of DR+ lymphocytes being significantly increased (p less than 0.005 and p less than 0.05, respectively). We thus conclude that in patients after splenectomy NK activity is decreased which may possibly be due to the lack of a NK subset. In contrast, the overall percentages of T cells (OKT11+), T helper/inducer (OKT4+) and T suppressor cells (Leu2a+) were significantly decreased in patients after splenectomy, although this defect could be compensated by a significant increase in the absolute lymphocyte number.     

Immunological reconstitution after bone marrow transplant with Campath-1 treated bone marrow.

Immunological reconstitution after allogeneic bone marrow transplant (BMT) was studied in 20 patients who received Campath-1 treated bone marrow. The peripheral blood lymphocyte phenotype was analysed with a panel of monoclonal antibodies at 3, 6 and 12 months. T cell proliferative capacity was evaluated by stimulation with PHA and Con A and in the mixed lymphocyte reaction (MLR). Natural killer (NK) cell activity was analysed against the K562 cell line at specified times after BMT in nine patients. Absolute numbers of T lymphocytes were reduced in all patients at 3 and 6 months. A marked decrease in the number of CD4+ cells persisted beyond 12 months. CD8+ cells regenerated more rapidly and reached normal at 6 months. No correlation was found between changes in lymphocyte subpopulations and the presence of graft-versus-host disease or cytomegalovirus infection. B cells recovered rapidly and maintained normal numbers throughout the study. A moderate increase in HNK1+ (Leu7) cells was observed at 3 and 6 months simultaneously with a low expression of NK15 (Leu11) and OKM1 antigens at 3 and 6 months, suggesting the presence of immature NK cells early after the transplant. A profound decrease of T cell proliferative capacity was observed both after mitogen stimulation and in the mixed lymphocyte reaction. NK cell activity was raised during the first month after transplant in all but one patient but no correlation was found with the presence of GVHD or cell marker analysis.     

Natural killer cells in Behçet''s disease.

We studied natural killer (NK) cell activity and numbers in the peripheral blood obtained from patients with Behçet''s disease (BD) in inactive and convalescent stage, and from healthy controls. Ratios of helper/suppressor cells (OKT4/OKT8) were below 1.0 in patients with active stage and were normal in the convalescent stage of BD. A relative increase of OKT8+ cells and at the same time of Leu 7+ cells was obtained in the active and convalescent BD stages. Double marker analysis revealed that the sub-population of cells expressing both the T8+ and the Leu 7+ antigen (T8+/Leu 7+) was increased in patients with active stage, and normal in the convalescent stage. The frequency of cells reactive with Leu 11 monoclonal antibody (active NK cells) was evaluated in patients with BD. Data from peripheral blood showed an increased sub-population of T8+/Leu 7+ double marker cells, and a decreased Leu 11+ cell sub-population in patients with active BD, but the majority of Leu 7+ cells in patients with convalescent stage lacked OKT8 antigen when investigated in a double marker system. A parallel increase of Leu 11+ cells was observed in the convalescent stage. This phenotypic analysis was carried out with the NK in vitro functional evaluation of cell populations from peripheral blood. NK cell activity in the clinically active stage of BD was significantly lower than that of healthy controls and patients in the convalescent stage. The decrease of peripheral blood NK function in patients with active BD may be related to the presence of immature forms of NK cells and/or to the increased percentage of T8+/Leu 7+ cells.     

Immunological analysis in familial common variable immunodeficiency

Immunological and genetic studies were performed in nine members from three generations of the family of a patient with common variable immunodeficiency (CVI). Two additional symptomatic members (mother and grandmother) had CVI. Among other six asymptomatic members, two had CVI and one had selective IgA deficiency. The proportions of monoclonal antibody defined total T cells (Leu 1+), helper phenotype (Leu 3+) suppressor phenotype (Leu 2+) T cells, natural killer cells (Leu 7+) and surface Ig+ B cells and proliferative response to phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and in mixed lymphocyte reaction (MLR) were comparable to controls. Addition of purified interleukin-2 (IL-2) resulted in augmentation of PHA-induced proliferation of T lymphocytes similar to that seen in the controls, however with IL-2 freshly isolated T cells in the absence of PHA demonstrated markedly increased proliferative response, suggesting the presence of in vivo activated T cells. Study of HLA phenotype did not reveal any linkage. This study demonstrates the genetic nature, possibly autosomal dominant inheritance, of common variable immunodeficiency; however the immunodeficiency is not linked to any specific HLA antigen.     

骨髓间充质干细胞抑制再生障碍性贫血患者外周血T细胞增殖的实验研究

背景：既往研究发现骨髓间充质干细胞具有免疫抑制作用,而再生障碍性贫血患者存在T淋巴细胞异常活化及增殖。 目的：体外分析骨髓间充质干细胞对再生障碍性贫血患者外周血T淋巴细胞增殖的抑制作用。 方法：分离再生障碍性贫血患者外周血T淋巴细胞,行羧基荧光素乙酰乙酸琥珀酰亚胺酯(CFDA SE)荧光染色,与体外培养扩增的骨髓间充质干细胞按3︰1比例直接接触法及Transwell法共培养,加入植物血凝素(PHA)刺激T淋巴细胞增殖,并设阴性及阳性对照。流式细胞术检测各组T细胞增殖情况,评价骨髓间充质干细胞对T淋巴细胞增殖的影响。 结果与结论：CFDA SE染色分析显示,直接接触组T细胞增殖较阳性对照组明显减低(P < 0.01);Transwell组T细胞增殖亦较阳性对照组减低(P < 0.05);直接接触组T细胞增殖较Transwell组明显减低(P < 0.01)。骨髓间充质干细胞可能通过直接接触及分泌某些细胞因子方式抑制再生障碍性贫血患者异常增殖的T细胞,以直接接触方式发挥主要作用。     

Correlation of natural killer cell function with Leu 7 reactivity in patients with humoral immunodeficiency.

We studied the surface markers Leu 7, Leu 1, Leu 2a and Leu 3a on lymphocytes of 54 healthy blood donors and 19 patients with humoral immunodeficiencies and compared the relative numbers of positive cells with the natural killer cell (NK) activity. In controls, and in 12 out of 19 patients (group A) the percentage of the Leu 7+ cells was positively correlated with NK activity. Seven of 19 patients had increased relative numbers of Leu 7+ cells and low NK activity (group B). In controls and group A patients about 40% of the Leu 7+ cells simultaneously expressed the cell markers Leu 1 and Leu 2a. In group B patients approximately 70% of the Leu 7+ cells carried T cell antigens. Furthermore, a distinct suppressor T cell predominance was noticed and the large granular lymphocytes of these patients showed morphological abnormalities.     

调节性T细胞及其分泌的细胞因子在再生障碍性贫血中的意义

目的:检测再障患者外周血中T细胞亚群比例及Treg细胞相关的细胞因子分泌水平,探讨其在再障发病中作用。方法:依据临床诊断标准,收集初发再障组、再障造血恢复组、正常对照组的外周血标本,流式细胞学方法检测各组CD4+、CD8+、NK、NKT、Treg细胞的比例,免疫磁珠法分离各组外周血中Treg细胞,并给予刺激培养,24、48小时后收集上清液,酶联免疫吸附试验(ELISA)检测Treg细胞分泌的细胞因子IL-10、IL-35、TGF-β的表达水平。结果:初发再障组的CD4+,Treg比例与正常对照组和再障造血恢复组相比显著低下;CD8+T细胞比例在再障患者中明显升高,其结果有统计学差异(P<0.05);NK、NKT的细胞与正常对照组比较无明显变化(P>0.05)。分离培养三组人群Treg细胞,ELISA检测结果显示:初发再障患者的IL-10、IL-35、TGF-β表达水平和正常对照组比较明显降低(P<0.05)。结论:T细胞免疫异常是再障发病机制的重要环节,Treg细胞在再障患者恢复造血过程中可能起着正向调控的作用。     

再生障碍性贫血患者外周血T细胞亚群和T细胞受体表达水平及其意义

采用流式细胞仪及间接免疫荧光法检测30例再生障碍性贫血患者外周血中T细胞亚群及T细胞表面受体表达水平,并与健康对照组相比,结果表明:70％再障患者存在CD4/CD8比例倒置及CD8~+％异常增高;50％再障患者外周血γδ-T细胞亚群及其在T淋巴细胞总体中所占比例均显著增高;而αβT细胞亚群及TirA~+细胞百分率与正常对照组相比无显著性差异。提示:半数以上再障患者外周血中存在异常增多的γδT细胞及Ts细胞亚群。并可通过其直接或间接作用抑制造血,从而导致再障的发生。     

Expansion of a minor subpopulation of peripheral blood lymphocytes (T8+/Leu 7+) in patients with haemophilia

Immunological analysis of peripheral blood mononuclear cells (PBM) was performed in 20 patients with haemophilia A or B. One of the patients had never received clotting factor substitution in his life. Six different sources of lyophilized clotting factor were used for the other patients, but every given patient received factor from one source, exclusively. None of the patients exhibited lymphadenopathy and only one suffered from local bacterial infection. Mononuclear cell counts were within the normal range and mitogen stimulation with phythaemagglutinin (PHA) and concanavalin A (Con A) was found normal in all but two patients. Ratios of helper and suppressor cells (T4/T8) were below 1.0 in 10 of the patients. Some of these patients had a relative increase of T8+ cells and at the same time of Leu 7+ (natural killer (NK)/suppressor) cells. Double-marker analysis revealed that the subpopulation of cells expressing both the T8 and the Leu 7 antigen, which on the average accounted for 2.1% of the mononuclear cells in controls, was increased 4.5 fold (9.1%) in haemophilia patients. One patient exhibited 37.8% T8+/Leu 7+ double-marker cells. VEP13+ cells (active NK cells) were decreased below the normal range in 11 of the patients. Abnormal values for lymphocyte subsets were found in every treatment group. The patient who had never received any clotting factor exhibited normal values in all respects. In an additional set of patients, those with increased percentage of T8+/Leu 7+ cells exhibited decreased NK cell activity indicating that the T8+/Leu 7+ cells are not active NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunoregulation of immunoglobulin production in normal infants and children.

Proportion of T cell subsets, spontaneous and PWM stimulated immunoglobulin production by peripheral blood lymphocytes and concanavalin A- (Con A) stimulated suppressor cell activity on immunoglobulin production by B cells was studied in 37 infants and children, to investigate changes of these parameters with age. Proportion of suppressor/cytotoxic (T8+) T lymphocytes was significantly lower in children below the age of 5 years, while there was no difference in proportion of total T lymphocytes (T3+) and helper/inducer (T4+) T cells. Spontaneous production and secretion of IgG and IgM by lymphocytes from children of all age groups was similar to that found in adults, but lymphocytes of children below the age of 10 years showed a low response to PWM stimulation. The activity of Con A-induced suppressor cells in inhibiting B cells producing immunoglobulins was almost absent in infancy, gradually increased during childhood and reached adult levels in teenagers. A significant association between the proportion of T8+ cells and Con A-induced suppression of B cell proliferation and a relationship between T4+ cells and spontaneous Ig production indicated the increasing maturity with respect to both number and function of peripheral blood lymphocyte subsets with advancing age.     

再生障碍性贫血T细胞亚群及NK细胞活性测定与疗效的关系

本文报道２０例再障患者ＣＤ３＋、ＣＤ４＋、ＣＤ４＋／ＣＤ８＋比值显著低于正常对照组（Ｐ＜０．０５），ＮＫ细胞活性显著低于正常对照组（Ｐ＜０．０１）。其中１０例经ＣＳＡ和ＡＯｄｒｉｏｌ（安雄）治疗，８例疗效好的患者ＣＤ４＋／ＣＤ８＋比值和ＮＫ细胞活性显著升高，提示测定ＣＤ４＋／ＣＤ８＋比值及ＮＫ细胞活性可作为观察再障疗效的一个指标。     

Immunological studies of autoimmune thyroid disorders: abnormalities in the inducer T cell subset and proliferative responses to autologous and allogeneic stimulation

Various immunological parameters were investigated in patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD). The total T cell numbers were significantly decreased in both diseases whether they were enumerated by E rosetting or by pan-T cell monoclonal antibodies (OKT3 and anti-Leu 1). This diminution was due to a loss in the inducer T cell subset (OKT4+/Leu 3a+) whereas the cytotoxic/suppressor T cells (OKT8+/Leu 2a+) were present at normal levels in both diseases. The B cells were significantly higher in GD patients than in controls but were not modified in HT patients. Monocyte percentages remained unchanged and DR+ cells were slightly increased in the two diseases. On the other hand, T lymphocyte responses to stimulation by autologous or allogeneic cells were significantly impaired in GD but not in HT whether cultures were performed in autologous plasma or AB serum. In addition, lymphocytes from normal subjects were unable to proliferate in auto- or allo-MLR in the presence of plasma from GD patients but they were reactive in the presence of HT plasma or AB serum. Taken together, these results suggest that the patients with autoimmune thyroid disorders exhibit a T cell imbalance within the OKT4+/Leu 3a+ subset. Moreover, this abnormality is correlated with the observation that autoreactive and alloreactive cells are defective in GD.     

Double phenotyping of immunoregulatory T cell subsets in patients with allergic asthma

In order to determine whether the dissection of helper/inducer (CD4 +) and suppressor/cytotoxic (CD8 +) lymphocyte subsets with Leu 8 reagent would reveal any differences between allergic asthma patients and non-atopic controls, we compared in both groups the 'true helper' T cell subset (Leu 8 - CD4 +), responsible for the major helper effect, and one of the suppressor T cell subpopulations (Leu 8 - CD8 +). Peripheral blood mononuclear cells from sixty-nine individuals, including nineteen extrinsic asthmatics, fifteen intrinsic asthmatics, seventeen patients with chronic obstructive lung disease and eighteen healthy controls, were comparatively analysed. Although total CD4 + cells and total CD8 + cells were similar for all groups, we found in the extrinsic asthma patients group a significant increase in the number of 'true helper' T cell sublineage (Leu 8 - CD4 +) and of suppressor cells expressing Leu 8 - CD8 + phenotype. Such imbalances may be implicated in the pathogenesis of atopic asthma.     

Impairments in functional subsets of T-suppressor (CD8) lymphocytes, monocytes, and natural killer cells among asbestos-exposed workers

Peripheral blood leukocytes from asbestos-exposed workers were analyzed by dual color flow cytometry using monoclonal antibodies that identify developmental (HLA-DR) and functional (Leu 8) subsets of T helper, suppressor lymphocytes, and monocytes. An increase in the number of T suppressor cells was closely associated with a decrease in T lymphocyte functions while numerical defects in activated monocytes (Leu M3+Ia+) and natural killer cells (Leu 7+) were correlated with a depressed Th/Ts ratio. Furthermore, among asbestos-exposed workers with depressed T cell functions we have demonstrated a significantly higher number of the effector Ts (Leu 2+ Leu 8-) subset which regulates both the Th/Ts lymphocyte system as well as B cells and NK cell activities. These findings identified changes in the T suppressor feedback regulatory loop as being responsible for the immunoregulatory imbalance among long-term asbestos workers. In double blind analyses of demographic and radiographic data these phenotypic changes were not correlated with age, smoking history, or duration of exposure but were associated with radiographic evidence of asbestos-associated effects. This correlation established a direct link between asbestos exposure and the subsequent development of immune dysfunction.     

Changes in the populations of lymphoid cells in human peripheral blood following physical exercise

Marked lymphocytosis occurs after exercise. In a study of healthy volunteers this was dominated by one population lacking T cell and B cell determinants and another expressing the Leu 2a phenotype (cytotoxic/suppressor). Lymphocytes from two individuals were characterised further and a near five-fold increase in cells expressing antigens associated with natural killer (NK) cells (Leu 7 and Leu 11) was noted. In addition, these emergent lymphocytes, unlike most T cells, lacked acid alpha-naphthyl esterase activity. In functional studies, exercise led to significantly greater NK activity but, in spite of altering the distribution of lymphocyte subpopulations, there was no detectable change in the proliferative response to the T cell mitogen, concanavalin A, over a wide range of cell concentration, mitogen dose and time. The numbers of low density macrophages and dendritic cells increased concomitantly with the increase in total lymphocytes. We conclude that exercise increases the proportion of circulating NK cells and cells expressing the Leu 2a phenotype.     

T lymphocyte subsets in the peripheral blood in patients with primary biliary cirrhosis

T lymphocyte subsets and natural killer (NK) cells in the peripheral blood of 10 patients with primary biliary cirrhosis (PBC) were examined by using various kinds of monoclonal antibodies directed to the surface markers of the lymphocytes. We found that the population of Leu 2a+, Leu 15- cytotoxic T cells was decreased in PBC patients compared to normal controls, especially in those with a high serum titer of anti-mitochondria antibodies. However, there was no significant difference in the population of Leu 2a+, Leu 15+ suppressor T cells between PBC patients and normal controls. Although the population of Leu 3a+, Leu 8- helper T cells was not significantly different, the population of Leu 3a+, Leu 8+ suppressor-inducer T cells was remarkably increased in PBC patients compared to normal controls. On the other hand, no such difference was seen for the NK cells. Furthermore, the Leu 3a+/Leu 2a+ ratio was significantly higher in PBC patients especially in those with a high serum anti-mitochondria antibody titer, which was thought to be due to the decreased population of cytotoxic T cells.     

Flow cytometric analysis of lymphocyte phenotypes in AIDS using monoclonal antibodies and simultaneous dual immunofluorescence

Simultaneous dual immunofluorescence and flow cytometry was used to study sixteen lymphocyte phenotypes in 209 men including: healthy homosexuals, lymphadenopathy patients (LAN), and AIDS patients. Significant differences between the distribution of lymphocytes in healthy homosexuals and healthy heterosexuals were decreased percentages of helper/inducer T cells (Leu 3), increased cytotoxic/suppressor T cells (Leu 2), and consequently a decreased Leu 3/Leu 2 ratio. The increased Leu 2 cells were identified as functionally cytotoxic subset Leu 2+ 15- phenotype rather than suppressor cells which are Leu 15+. Leu 2 and Leu 3 bearing cells exhibited an excess of membrane-bound immunoglobulins which were easily elutable at 37 degrees C. An increased percentage of an HLA-DR framework determinant bearing T cells were also detected. Within the NK cell family, Leu 7 cells were moderately increased and the functionally unidentified Leu 2+ 7+ population was strikingly elevated. LAN or AIDS patients were compared to healthy homosexual controls. Lower percentages of Leu 3 cells and higher percentages of Leu 2 cells were evident in LAN patients. These subsets were similar in LAN and AIDS patients. The increase in Leu 2+ cells was due to the Leu 2+ 15- cytotoxic subset. Fewer T cells had immunoglobulin in LAN and AIDS. A definite increase in Leu 2+ DR+ cells but not Leu 3+ DR+ cells occurred in AIDS compared to LAN or healthy controls. NK cell changes already present in healthy homosexuals persisted in LAN and AIDS patients. No differences in the distribution of B cells was detected in any intergroup comparisons. Changes in monocytes or pan-T cells were relatively insensitive measures of immunologic alterations among any of the groups. These results indicate many of the changes in lymphocyte subsets seen in AIDS and LAN subjects are already present in a carefully screened population of healthy homosexuals in San Francisco. Many of the changes in Leu 2 and NK family of cells suggest a possible adaptive response to viral or neoplastic challenge. Whether these interesting phenotypic alterations relate to functional changes in response to such challenge of the identified subsets waits further investigation.     

Bone marrow transplantation in man. Analysis of T and B cell functions in PWM driven Ig production.

The functional activity of B and T lymphocytes from the blood of eight patients, who had successfully been treated with allogeneic bone marrow for severe aplastic anaemia or acute leukaemia, was studied in pokeweed mitogen (PWM) driven polyclonal immunoglobulin synthesis. Activity of B cells was measured as IgM and IgG synthesis by a standard number (40 X 10(3] of patient lymphocytes in the presence or absence of healthy donor T cells. In addition, the frequency of PWM reactive B cells, giving rise to IgM and/or IgG producing daughter cells, was estimated by limiting dilution analysis. With this method, it was found that only a small percentage (1-3%) of peripheral blood B cells from healthy individuals is reactive to PWM. In the patients, both parameters for B cell reactivity were decreased during the first 40 weeks after bone marrow transplantation. As parameters for T cell activity, help and suppression on the Ig production by healthy donor lymphocytes were tested. In most patients, T helper cell activity was strongly decreased, whereas some patients had excessive T suppressor cell activity. The observed functional activities were only partially correlated with the marker profile of the T cell populations, as detected by reactivity with monoclonal antibodies. Each patient had a distinct, individual pattern of reconstitution of these functions. There was no positive correlation between Ig production in vitro and the capacity to form antibodies in vivo, nor between the other in vitro findings and clinical features, such as the occurrence of infections or graft versus host disease.     

Suppressive role of NK cells in pokeweed mitogen-induced immunoglobulin synthesis: effect of depletion/enrichment of Leu 11b+ cells.

Natural killer (NK) cells probably have immunoregulatory effects. However, the evidence to date is mainly based on the suppressive effect of enrichment with relatively impure NK populations (large granular lymphocytes, LGL, Leu 7a+ cells). Here we report on the effect of enrichment and depletion of Leu 7a+ and Leu 11b+ cells (the latter containing virtually all NK activity in freshly prepared lymphocytes) on pokeweed mitogen (PWM)-induced immunoglobulin (Ig) synthesis. Enrichment suppressed Ig synthesis to a degree dependent on the number of cells added, and was not enhanced further by their pretreatment with interferon. Furthermore, depletion of Leu 11b+ cells from peripheral blood lymphocytes (PBL) led to marked enhancement (2-25-fold increase) of Ig synthesis, suggesting these cells may normally exert a suppressive effect. The possible underlying mechanisms were investigated further. Enhanced Ig synthesis by Leu 11b-depleted cultures was associated with an increased number of Ig-secreting cells by plaque assay, but with no change in numbers of CD4+ or CD8+ cells. Treatment of PBL with monoclonal antibodies (anti-Leu 7a/Leu 11b) alone suppressed PWM-induced immunoglobulin synthesis. We conclude that NK cells play a role in the regulation of Ig production, at least in part by an effect on activation/differentiation of B cells, but independent of altered T-cell subpopulations. The effect may be unrelated to their cytotoxic function (being unaffected by interferon, IFN), although the direct effects of anti-Leu 11b and Leu 7a in enhancing the suppressive effect suggest an alternative activation pathway.     

Decreased TcR-CD3+ T cell numbers in healthy aged humans. Evidence that T cell defects are masked by a reciprocal increase of TcR-CD3- CD2+ natural killer cells

While there is accumulating evidence to indicate the presence of functional abnormalities in T cells from aged healthy humans, their cellular basis remains unclear. By using two-color immunofluorescence and multiparameter flow cytometry we show that (a) the number of peripheral blood antigen receptor-positive (TcR-CD3+) T cells is significantly lower in aged than in young adults; (b) the numbers of E-rosette-forming (CD2+) cells are maintained in the elderly due to a reciprocal increase in the frequency of TcR-CD3- cells, which constitute only a minor lymphocyte subpopulation in young adults, and (c) TcR-CD3-CD2+5- lymphocytes exhibit the phenotypic features of natural killer (NK) cells. By using functional assays we show the TcR-CD3-CD2+16+ lymphocytes are indeed NK cells because they are activated by and lyse NK targets. In contrast, they are unresponsive to either phytohemagglutinin or mitogenic CD2 monoclonal antibody stimulation, which in turn activates TcR-CD3+CD2+16- T cells. We conclude that the increase in TcR-CD3-CD2+ NK cells masks the T cell reduction in aged humans by normalizing CD2+ cell frequencies. However, NK cells cannot functionally substitute the thymus-derived lymphocytes they replace.