Cells with Fc gamma receptors from normal donors suppress granulocytic macrophage colony formation

We investigated the role of normal human marrow cells with Fc receptors for IgG (Fc gamma+) on autologous granulocyte-macrophage colony (GM- CFC) formation. It was found that Fc gamma+ normal human marrow cells, both with (E+) or without receptors for sheep erythrocytes suppressed GM-CFC at as low a concentration as 0.25 X 10(5) cells/ml of culture. A similar effect was observed with E- Fc gamma+ but not E+ Fc gamma+ peripheral blood cells. Suppression by Fc gamma+ cells did not require mitogen activation and was not inactivated by irradiation (2000 R). This report presents a new in vitro regulatory mechanism for GM-CFC growth in normal donors.     

Natural killer (NK) cell activity of peripheral blood, synovial fluid, and synovial tissue lymphocytes from patients with rheumatoid arthritis and juvenile rheumatoid arthritis.

Natural killer (NK) cell activity was investigated in peripheral blood, synovial fluid, and synovial tissue lymphocytes from patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). Unfractionated lymphocytes, T lymphocytes, and non-T lymphocytes from the 3 compartments of JRA patients had reduced activity compared with that of normal peripheral blood lymphocytes (with p values usually between 0.05 and 0.1). Unfractionated synovial tissue lymphocytes of RA patients also showed reduced cytotoxicity (0.05 less than p less than 0.1), whereas peripheral blood lymphocytes exerted normal NK cell activity. The NK activity was exerted by cells both with and without Fc gamma receptors. The highest cytotoxicity was observed in Fc gamma receptor-positive cells, both in peripheral blood and synovial fluid, since more than 70% reduction in NK activity was found after depletion of Fc gamma receptor-positive cells. No evidence of lymphocytotoxic antibodies or other factors with influence on NK cells was observed in the patients' sera.     

Different E-rosetting properties of human peripheral blood NK- and K-cells

Mononuclear, non-adherent blood leukocytes were separated into the spontaneously E-rosetting (E+) and non-E-rosetting (E-) fraction. NK- and K-cell activity was determined simultaneously in a 4 h assay against 51Cr-labeled K 562 cell line cells and rabbit antiserum coated mouse leukemia cells (Gr/E) respectively. In each case E- exhibited a significantly higher K-cell activity than E+ [M16 donors E-:E+ = 46 +/- 11:10 +/- 6 (% specific cytotoxicity)]. With regard to NK-cell activity E- of only 7 donors was significantly more active than E+ [M7 donors E-:E+ = 49 +/- 15:20 +/- 10]. Six times the activities of the two fractions were not significantly different [M6 donors E-:E+ = 46 +/- 15:39 +/- 14]. On the other hand E+ of 3 donors displayed a significantly stronger activity than E-[M3 donors E-:E+ = 13 +/- 10:36 +/- 9]. These results confirm the heterogeneity of NK-cells with respect to E-rosetting properties and indicate that NK- and K-cells of at least 3 donors may belong to different cellular subsets [NK:E- less than E+; K:E- greater than E+].     

Natural killer cell activity in inflammatory joint disease

The natural killer (NK) cell activity of unfractionated peripheral blood and synovial fluid mononuclear cells from patients with inflammatory joint disease was measured in a short-term assay using the human tumour cell line, K562, as the target. The mean values for peripheral blood NK activity of the various groups (controls, rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA] were similar although the rheumatoid group showed the widest range. However, the NK activity of PsA patients (23.74 +/- 10.14) was significantly lower than that of the controls (31.63 +/- 10.8, 0.05 greater than P greater than 0.01). Almost without exception, NK activity was found to be considerably lower in synovial fluid than in paired blood samples (p less than 0.01).     

CD16- CD56+ natural killer cells after bone marrow transplantation.

Natural killer (NK) cells are phenotypically defined as lymphocytes expressing the antigens CD56 and mostly CD16 (Fc gamma RIII), but lacking CD3. A small CD3- CD16- CD56+ NK cell subset has been described in normal individuals representing less than 2% of peripheral blood lymphocytes. We analyzed here 70 patients for their reconstitution of the immune system during follow-up after autologous or allogeneic bone marrow transplantation. In 35% of these patients, two different NK cell subsets, namely CD56+dim and CD56+bright cells, were observed. The mean duration of these two subsets after transplant was 4 months. Sixty-five percent of the patients exhibited an increased number of NK cells, but only the typical CD16+ CD56+dim population. The CD56+bright subpopulation represented a particular CD3- CD16- NK subset, with posttransplant frequencies up to 70% of all NK cells and 40% of peripheral blood lymphocytes, respectively. In contrast to normal CD56+dim NK cells, CD56+bright cells coexpressed the activation antigens p75 beta-chain of interleukin-2 receptor (IL-2R), CD2R, and CD26, but were negative for CD16. NK and antibody-dependent cellular cytotoxicity activity of CD56+bright cells was low compared with CD56+dim NK cells. But using IL-2 and interferon gamma, their cytotoxicity could be enhanced even more than in CD56+dim lymphocytes. These different subsets may reflect distinct activation or differentiation steps of NK cells during reconstitution of the immune system. Their differential response to IL-2 may be of functional importance for posttransplant cytokine therapy.     

Suppressed natural killer cell activity in patients with chronic autoimmune thrombocytopenic purpura

Natural killer (NK) cell activity was studied in 17 patients with primary chronic idiopathic autoimmune thrombocytopenic purpura (ATP). Fifteen of 17 patients had a significantly reduced NK cytotoxicity against 51chromium labeled K562 target cells (mean LU20% = 18 +/- 20 in patients versus 65 +/- 25 in controls, P less than 0.001). NK activity was also significantly reduced in all of six patients with secondary ATP as compared with normal controls (LU20% 28 +/- 15, respectively, P less than 0.005). The NK activity in both patient groups correlated with the duration of therapy being received (r = 0.60, P less than 0.001). Immunophenotypic analysis of peripheral blood mononuclear cells from patients with ATP revealed that CD8- cells bearing CD57 (HNK-1, Leu 7) and CD3- cells bearing CD56 (Leu 19) were quantitatively within the normal range. These findings indicate that patients with ATP have a functional defect in NK cytolytic activity.     

Effect of recombinant gamma interferon on natural killer cell activity in patients with gastric cancer

We investigated the effect of recombinant interferon-gamma (rIFN-gamma) in vitro on natural killer (NK) cell activity of peripheral blood lymphocytes (PBL) in patients with gastric cancer. Thirty untreated patients with gastric cancer and eleven healthy donors were studied. NK cell activity in healthy donors was 38.6 +/- 5.2%. In patients with gastric cancer, NK cell activity was 32.4 +/- 3.9% in stage I, 35.5 +/- 7.1% in stages II and III, and 22.4 +/- 3.9% in stage IV. NK cell activity in stage IV patients was significantly lower than in healthy controls or gastric cancer patients in stages I-III. After stimulation by rIFN-gamma, NK cell activity increased in all groups, and in stage IV patients NK cell activity recovered to normal levels. However, there was no significant increase in the proportion of Leu 7 positive or Leu 11 positive cells in PBL. In conclusion rIFN-gamma enhances the activity of NK cells, but does not increase the number of active NK cells.     

Clinical signification of natural killer activity in B-cell chronic lymphocytic leukemia

The natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) and lymphocytes with the capacity to form stable rosettes with neuraminidase-treated sheep red blood cells (E+) was studied in 28 previously untreated patients (11 at stage 0, 10 at stage I and 7 at stages II and III, according to Rai's classification) and 7 treated patients with B-cell chronic lymphocytic leukemia (B-CLL), all of them at stage 0 according to Rai's classification after treatment, and in 15 healthy controls. The mean NK activities of PBMC and E+ lymphocytes from untreated patients were significantly decreased (p less than 0.001) when compared with those of PBMC and E+ lymphocytes, respectively, from healthy controls. However, PBMC and E+ cells from treated patients demonstrated NK activity similar to that of the corresponding cellular populations of controls (p greater than 0.05). Furthermore, there were no significant differences among the NK activities of E+ lymphocytes from untreated B-CLL patients in the different clinical stages 0, I, II and III, according to Rai's classification (p less than 0.05). These results demonstrate that the very low or undetectable levels of NK activity present in PBMC and E+ cell populations from previously untreated patients with B-CLL, regardless of the clinical stage of the disease, can be modified by systemic therapy with alkylating agents. Moreover, the NK activity of PBMC and E+ lymphocytes from some treated patients that have achieved the stage 0 according to Rai's classification after chemotherapy can be found within the range of the lytic activity shown by PBMC and E+ cells from normal donors.     

Malignant T gamma/delta lymphoproliferative disease with natural killer lytic activity.

A 17-year-old girl presented with a lymphoproliferative disease involving the bone marrow, peripheral blood, and liver associated with reactive hyperplasia of the spleen. Neoplastic cells were atypical medium-sized lymphoblasts with convoluted nuclei and nucleoli without features of large granular lymphocytes (LGL). The phenotype was CD3+ CD4- CD8-, TCR alpha/beta-, TCR gamma/delta+, delta TCS1-, and CD16+, and these cells exhibited spontaneous natural killer (NK) activity. DNA analysis showed rearrangement of the TCR gamma gene but not of TCR beta or of Ig mu genes. This unusual lymphoproliferative disease may represent the neoplastic expansion of a minor subset of normal T gamma/delta cells with NK activity.     

Severe deficiency of natural killer activity in the peripheral blood of patients with hairy cell leukemia

Natural killer (NK) activity against K-562 tumor cells was evaluated in peripheral blood leukocytes (PBL) obtained from untreated patients affected by hairy cell leukemia (HCL). NK activity present in PBL from 10 HCL patients was at least six-fold lower (p less than 0.01) than that present in PBL from 15 healthy donors. Decreased NK activity in HCL PBL was not due to dilution of the NK effector cells by the neoplastic cells; in fact, NK activity of PBL from 4 HCL patients with less than 5% circulating neoplastic cells was still five-fold lower (p less than 0.01) than that present in normal PBL. Partial characterization of the NK defect in HCL patients indicated that: (A) defective cytotoxicity was not dependent on the duration of the assay; (B) HCL PBL added to normal PBL during the assay did not exert suppressor activity; (C) the NK activity of HCL PBL could be potentiated in vitro by interferon; and (D) low levels of NK activity were associated with reduced numbers of circulating monocytes (p less than 0.01) and of large granular lymphocytes (LGL) (p less than 0.01). In conclusion, our results indicate that the low levels of NK activity present in the peripheral blood of HCL patients may be related to reduced numbers of circulating effector cells.     

Production of colony-stimulating activity by human natural killer cells: analysis of the conditions that influence the release and detection of colony-stimulating activity

Highly purified natural killer (NK) cell suspensions were tested for their capacity to release colony-stimulating activity (CSA) in vitro. NK cell suspensions comprised primarily CD16+ cells and were devoid of CD3+ T cells, CD15+ monocytes, and of B cells. CSA was detected in the NK cell supernatants and sustained the growth of myeloid colonies from both normal peripheral blood and bone marrow. CSA could be in part inhibited by pretreating NK cell culture supernatants with a specific goat anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antiserum. The inhibition, however, was never complete, a finding that suggests that additional factors were responsible for CSA. Incubation of NK cells with K562 cells (an NK-sensitive target) or with normal bone marrow cells resulted in the appearance of a strong colony- inhibiting activity (CIA) in the culture supernatants. Such CIA was demonstrable in an experimental system where bone marrow or peripheral blood progenitors were induced to form myeloid colonies in the presence of conditioned medium by CSA-producing giant cell tumor (GCT) cells. Stimulation of NK cells with NK-insensitive targets failed to induce CIA production. Neutralizing antitumor necrosis factor (TNF) monoclonal antibodies (MoAbs) were found capable of inhibiting CIA present in the supernatants of NK cells stimulated with K562 cells. Following treatment with anti-TNF antibodies, CSA was again detectable in the same supernatants. This finding indicates that induction of TNF production did not concomitantly switch off CSA production by NK cells. Pretreatment of NK cells with recombinant interleukin-2 (rIL-2) or gamma interferon (r gamma IFN) did not change the amount of CSA released. However, treatment with rIL-2 caused the appearance of a factor in the NK cell supernatants capable of sustaining the formation of colonies of a larger size.     

Natural killer cell activity in cigarette smokers and asbestos workers

In order to evaluate the effects of cigarette smoking and asbestos exposure on cellular immunity, we tested a group of cigarette smokers and asbestos workers for natural killer (NK) activity in the peripheral blood. The mean NK activity in cigarette smokers was lower than in normal subjects (13.7 +/- 1.6 versus 29.0 +/- 3%; p less than 0.05). As a group, the mean NK activity for the asbestos-exposed group was also reduced compared with that of the nonsmoking control group (22.6 +/- 3.2%; p less than 0.05). When divided according to the smoking status, the asbestos workers who were nonsmokers or ex-smokers showed similar decreases in NK activity compared with normal subjects (19.5 +/- 6.2 and 21.2 +/- 4.5%, respectively; p less than 0.05). A subgroup of asbestos-exposed subjects who currently smoked showed no decrease in NK activity. The data show that NK activity is reduced in the peripheral blood of cigarette smokers and asbestos workers. The relatively normal NK activity found in asbestos workers who also smoked is unexplained. Impairment of NK activity is a potential mechanism for the increased incidence of infection and cancer in smokers and neoplasia in asbestos workers.     

Decreased natural killer cell activity versus normal natural killer cell markers in mononuclear cells from patients with smouldering leukemia

Peripheral blood (PB) and bone marrow mononuclear cells from 23 patients with smouldering leukemia were analyzed for natural killer (NK) cell activity and various surface cell markers. Significantly reduced NK activity was detected in the patients' PB compared with the activity in the healthy controls (p less than 0.0005). A similar difference in NK cell activity between the 2 groups was also observed in bone marrow mononuclear cells (p = 0.005). In contrast, no significant differences in cells positive for the NK cell markers Leu-7 and Leu-11b were found between patients and controls, either in PB or in bone marrow. The patients' PB and bone marrow mononuclear cells had, however, a reduced percentage and absolute number of Leu 3a+ and T8+ cells. Patients with smouldering leukemia have immunological derangements which may make them predisposed for the later development of florid leukemia.     

Discrepancy between phenotypic and functional features of natural killer T-lymphocytes in B-cell chronic lymphocytic leukaemia

The phenotypic expression and functional capacity of natural killer (NK) T-lymphocytes (E+, OKT3+) were analysed in a series of untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL). The mean value of NK activity of B-CLL T-lymphocytes, tested against the K562 cell line, was significantly depressed (P less than 0.01) in the 20 cases studied, compared with that of normal T-cells. Incubation with human leucocyte interferon produced an increase (P less than 0.05) in NK activity, although the mean value was still significantly lower (P less than 0.05) than that obtained with normal T-cells. Furthermore, the formation of effector-target conjugates was significantly lower (P less than 0.01) among B-CLL T-cells compared with normal T-lymphocytes. Despite the reduced NK functions observed in the majority of B-CLL patients, the capacity of T-cells to react with the monoclonal antibody (MoAb) Leu-7 (HNK-1 clone), assessed in 60 patients, was significantly higher (P less than 0.001) in B-CLL than in normal blood (mean 24% +/- 10.6 SD v 9% +/- 4.2), irrespective of the clinical stage of the disease. These findings suggest that the reduced cytotoxic ability of B-CLL T-lymphocytes may be due either to an expanded population of immature T-cells which already express a cytotoxic-like phenotype (E+, OKT3+, HNK-1+) but which lack adequate cytotoxic functions, or, alternatively, to an intrinsic defect of the natural effectors present within the T-cell population of B-CLL. The T-cell functional abnormalities documented in this study, together with other defective functions previously described, may be implicated in some of the complications frequently associated with B-CLL, particularly the high incidence of secondary neoplasms. There is growing evidence that natural cytotoxicity may play a major role in the immune surveillance system, both against tumour cells and virus-infected cells (Herberman & Ortaldo, 1981). Natural killer (NK) cells are a morphologically homogeneous population of large granular lymphocytes with azurophilic granules in the cytoplasm (Timonen et al, 1981), which are non-adherent and express receptors for the Fc portion of IgG. About 50% of these cells form rosettes with sheep red blood cells (E-rosettes) (West et al, 1977). A monoclonal antibody (MoAb) which appears to react with practically all human NK cells (HNK-1 clone, Leu-7; Becton Dickinson) has been recently produced (Abo & Balch, 1981).(ABSTRACT TRUNCATED AT 400 WORDS)     

肝脏自然杀伤细胞在小鼠急性肝衰竭中的作用

目的 探讨肝脏自然杀伤(NK)细胞在3型鼠肝炎病毒(MHV-3)诱导的小鼠急性肝衰竭中的作用.方法 取6～8周龄雌性Balb/cJ小鼠,腹腔注射100 pfu MHV-3,采用流式细胞术检测感染MHV-3 0、24、48、70 h后的Balb/cJ小鼠肝脏、脾脏、外周血和骨髓中NK细胞的百分率及肝脏NK细胞表面活化分子CD69表达的百分率.细胞内细胞因子染色法检测肝脏NK细胞分泌干扰素γ的水平.非放射性细胞毒试验检测肝脏NK细胞的杀伤活性. 结果Balb/cJ小鼠感染MHV-3后,肝脏NK细胞的比例显著升高,在感染48 h后达到峰值(43.9%±2.3%),约为感染前的4倍,随后仍维持在较高水平至小鼠死亡;外周血NK细胞比例同样明显升高,在感染48 h后达到峰值(18.0%±5.4%),但随后显著同落,至70 h仅为1.3%±0.6%,脾脏和骨髓NK细胞比例均先明显减少后又有所上升.肝脏NK细胞在MHV-3感染48 h后其表面活化分子CD69表达明显上调,杀伤活性显著增强,同时分泌干扰素Y的水平也显著增加. 结论 Balb/cJ小鼠感染MHV-3后,来自骨髓和脾脏的NK细胞在肝脏迅速大量募集和活化,且杀伤活性显著增强,分泌干扰素Y水平也显著增加,表明肝脏NK细胞在MHV-3导致的急性肝衰竭中可能发挥着关键作用.     

Absence of circulating natural killer (NK) cells in a child with erythrophagocytic lymphohistiocytosis lacking NK cell activity

A 5-year-old girl who was diagnosed as having erythrophagocytic lymphohistiocytosis died at age 9 years. Peripheral lymphocytes from the patient persistently lacked natural killer (NK) cell activity during the 4-year observation period: the percent lysis values as measured by a 4-hr 51Cr release assay at a 40:1 effector:target ratio were below 1.0% against K562 and Molt-4 cells as compared with the normal lymphocyte value (mean +/- SD) of 46.2% +/- 5.8% and 43.9% +/- 6.7%, respectively. The patient's lymphocytes never developed NK cell activity by their incubation with target cells for longer time periods or by their stimulation with interferon-alpha, interleukin-2, or polyinosinic-polycytidilic acid. Single cell-in-agarose assay showed the absence of target-binding cells (TBCs): TBC numbers were below 0.3% as compared with the normal lymphocyte value of 8.1% +/- 1.3% (mean +/- SD). Flow cytometry showed a marked decrease in Leu-7+ cells (1.7%) and the absence of Leu-11+ cells (0.4%) in the peripheral blood. These results first demonstrate a case of erythrophagocytic lymphohistiocytosis in which there is the lack of NK cell activity due to the absence of circulating NK cells.     

Lymphocyte subset distribution and natural killer cell activity in men with idiopathic hypogonadotropic hypogonadism

Sex-related differences in immune responsiveness are mediated at least in part by sex steroid hormones. Lymphocyte subset distribution in peripheral blood and natural killer cell function both have been reported to be under hormonal control. In order to gain more insight into sex steroid hormone action on the immune system, we have measured the lymphocyte subset distribution and natural killer cell activity in 18 men with idiopathic hypogonadotropic hypogonadism before treatment, and after hormonal treatment had normalized plasma testosterone levels. In untreated patients, the mean plasma testosterone concentrations were significantly lower than those in the treated men (3.0 +/- 0.5 nmol/l vs 16 +/- 1.7 nmol/l, p less than 0.001). The percentage of peripheral CD3+ lymphocytes, CD8+ cells, the CD4+/CD8+ ratio, and the natural killer cell activity of peripheral mononuclear cells measured in a 51Cr release assay against target K 562 cells did not differ between patients with idiopathic hypogonadotropic hypogonadism and healthy adults, and most importantly, did not change during hormonal treatment which normalized plasma testosterone levels in the patients. In contrast, the percentage of peripheral CD4+ cells was significantly higher in untreated patients compared with normal adult subjects or patients with idiopathic hypogonadotropic hypogonadism after hormonal treatment that resulted in normal plasma testosterone levels (53 +/- 2 vs 47 +/ 2, p less than 0.05). It should be noted that the percentage of peripheral CD16+ cells was significantly lower in untreated men with low plasma testosterone levels than in normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local immune mechanisms in inflammatory bowel disease and colorectal carcinoma. Natural killer cells and their activity

Mononuclear cell (MNC) populations isolated from intestinal mucosa, mesenteric lymph nodes, and peripheral blood have been assessed for their natural killer (NK) (Leu-7+) cell proportions and NK cell activity against K-562 erythroleukemic target cells. In peripheral blood, normal proportions of Leu-7+ cells were found in patients with Crohn's disease or ulcerative colitis, whereas increased proportions in colorectal carcinoma may have been related to the higher mean age of these patients. Low proportions of Leu-7+ cells (less than 3%) were present in intestinal MNCs in Crohn's disease, ulcerative colitis, colon cancer, and miscellaneous intestinal diseases. All groups of patients had diminished NK activity of peripheral blood MNCs compared with a group of healthy controls. Intestinal NK cell activity from histologically normal mucosa correlated with autologous peripheral blood NK cell activity (p less than 0.001) but no such correlation was seen for patients with inflammatory bowel disease. Mucosal or nodal NK cell activity showed a wide range of activity but did not relate to the underlying disease, mucosal histopathology, drug therapy, or, in patients with cancer, Dukes' grading. Intestinal MNCs from all patient groups responded to stimulation with lymphoblastoid interferon, except in a small number of patients whose unstimulated activity was not detectable. In conclusion, the NK cell on intestinal mucosa behaves similarly in various intestinal diseases. However, the disparity between NK activity of autologous peripheral blood and intestinal MNCs in inflammatory bowel disease highlights the difficulty in extrapolating peripheral blood findings to mucosal immune events.     

Characterization of natural killer cells with antileukemia activity following allogeneic bone marrow transplantation

To identify cells with potential antileukemia activity following bone marrow transplantation, we have monitored immunologic reconstitution in a patient with acute lymphocytic leukemia in second remission who received intensive chemotherapy and total body irradiation followed by infusion of allogeneic histocompatible marrow. Prior to transplantation, donor bone marrow cells were depleted of T lymphocytes by in vitro treatment with anti-T12 monoclonal antibody and rabbit complement. In the first 3 weeks following bone marrow transplantation, the predominant regenerating mononuclear cell population in peripheral blood exhibited a phenotype characteristic of natural killer (NK) cells. After 4 weeks, T lymphocytes became predominant, but NK cells persisted. Cultured peripheral blood lymphocytes obtained 12 weeks posttransplant were able to display significant cytotoxicity against leukemic blasts that had been cryopreserved at the time of relapse 5 months prior to bone marrow transplantation. To further characterize those cells with antileukemia activity, we used in vitro cloning techniques to identify four monoclonal populations, termed TC12, -48, - 50, and -59, with strong antitumor activity. Cytogenetic analysis demonstrated that each clone was of donor origin. Phenotypic characterization showed that the four clones expressed NKH1A but did not express T3, T4, or T8 antigens. Three of the four clones expressed T11/E rosette antigen. Each clone exhibited strong cytotoxicity against genetically unrelated hematopoietic tumor cell lines such as K562, Molt- 4, JM, and U937. In addition, we found that these patient clones were similar to cloned NK cells previously derived from normal individuals. Taken together, these results suggest that at least some clones with antileukemia activity following bone marrow transplantation are cells with NK-like function and phenotype. Functional analysis of these cytolytic cells in larger numbers of patients will be necessary to determine the clinical significance of this finding.     

Natural killer cell activity and T subpopulations in thalassemia major

Natural killer (NK) cell activity against K562 cell targets and the distribution of T cell subpopulations were investigated in the peripheral blood of 25 patients affected by beta thalassemia major, 18 clinically healthy heterozygotes, and 25 age-matched normal subjects. It was found that thalassemia major patients display augmented levels of NK activity [specific lysis 41.9 +/- (se) 4.5%], while thalassemic carriers behave as normal controls [specific lysis 34.6 +/- (se) 3.5%]. The increase of NK function was neither related to the splenectomy nor to the siderosis, but rather to the age and the amount of blood units that the patients had received. An imbalance of circulating T subsets with the helper/suppressor cell ratio significantly diminished (p less than 0.001) was also detected in homozygotes but not in carriers. The finding that NK function is enhanced in homozygous beta thalassemia might be of clinical interest in assessing the risk of development of malignancies in these patients.