Discrepancy between phenotypic and functional features of natural killer T‐lymphocytes in B‐cell chronic lymphocytic leukaemia
Authors: Foa R. , Lauria F. , Lusso P. , Giubellino M. C. , Fierro M. T. , Ferrando M. L. , Raspadori D. , MATERA L. 
Published: March 2008

Summary. 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&<0‐01) in the 20 cases studied, compared with that of normal T‐cells. Incubation with human leucocyte interferon produced an increase (P&< 0‐05) in NK activity, although the mean value was still significantly lower (P &< 0‐05) than that obtained with normal T‐cells. Furthermore, the formation of effector‐target conjugates was significantly lower (P&<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&<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). Purification experiments have shown that in man the NK activity is present within two distinct HNK‐1 positive lymphocyte subsets: HNK‐1+, OKT3 (pan T)‐, OKMl (myelo‐monocytic antigen)+ and HNK‐1 +, OKT3 +, OKMl‐ (Abo et al, 1982).

Abnormal levels of natural cytotoxicity have been reported in numerous human conditions. More recently the abnormal proliferation of T‐cells with NK function has been reported in cases of acute and chronic T‐cell leukaemias (Komiyama et al, 1982: Itoh et al, 1983).

B‐cell chronic lymphocytic leukaemia (B‐CLL) is a neoplastic disorder characterized by the progressive accumulation of monoclonal B‐lymphocytes (Preud'homme & Seligmann, 1972), often complicated by severe hypogammaglobulinaemia (Foa et al. 1979) and by a high risk of second tumours (Hyman, 1969). Recent evidence indicates that, together with the neoplastic B‐cell proliferation, several phenotypic and functional abnormalities can be encountered within the residual T‐cell population (Kay et al, 1979; Chiorazzi et al, 1979; Lauria et al, 1980; Foa et aZ, 1980; Davis, 1981). This has lead several authors to suggest that these abnormalities may play a role in the progression of the disease and in the development of some of its complications. In view of this we have tested the reactivity of the T‐cell enriched population from 60 cases of B‐CLL with the HNK‐1 MoAb. In a series of patients the phenotypic analysis was compared with the NK activity measured in a chromium release assay, before and after pre‐incubation with human leucocyte interferon (IFN), and by the capacity to form conjugates with NK sensitive target cells.