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

Abstract

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)

Analysis of CD16+CD56dim NK cells from CLL patients: evidence supporting a therapeutic strategy with optimized anti-CD20 monoclonal antibodies

“…14 Several studies have reported functional alterations in NK cells in these patients, including defective cytotoxic activity, which are particularly pronounced in advanced disease and that could be because of the accumulation of leukemic cells rather than to any intrinsic defect in the former. 15,16 This hypothesis was suggested by the restoration of their functional activity after interferon (IFN)-a and/or interleukin (IL)-2 treatment. 17,18 We conducted the first extensive characterization of the phenotypic and cytotoxic qualities of NK cells from CLL patients and compared them with those of healthy subjects.…”

Cytotoxic lymphocytes in B-cell chronic lymphocytic leukemia

“…A large percentage of the CD 4 ÷ lymphocytes coexpress NK lineage markers [24]. Also, the CD 57 antigen is present on a significantly higher part of the T-lymphocytes in B-CLL patients in comparison with healthy donors [5]. Functional studies on T lymphocytes from B-CLL patients give contradictory results [1,3,4, 6, 7, 9 -1 3 , 17, 18].…”

Expansion of natural killer (NK) and natural killer-like T (NKT)-cell populations derived from patients with B-chronic lymphocytic leukemia (B-CLL): a potential source for cellular immunotherapy

“…A dilutional effect of leukemic cells and intrinsic functional defects on NK cells have been implicated. 16,20,21 These abnormalities found in NK cells might allow the appearance and/or maintenance of the leukemic B-cell accumulation. However, defective NK activity has been shown to be restored by interferon (IFN)-a and IL-2.…”