Defective expression of T cell antigens in chronic lymphocytic leukaemia: relationship to T cell dysfunction.
In chronic lymphocytic leukaemia (CLL) peripheral blood T cells have a variety of functional abnormalities. To explore more extensively the T cell status of B-CLL patients, surface immunoglobulin-negative cells were isolated by sheep erythrocyte rosetting (ER) and the membrane phenotypes of the ER + cells defined by immunofluorescence utilizing monoclonal antibodies (MAb). In 11 of 18 CLL patients (CLL group I) there was excellent correlation between ER + and T3 (mature T cell marker) positivity. In the remaining patients (CLL group II), only 5-45% of ER + cells were T3 positive, suggesting that many rosetting cells were non-T. However, the ER +, T3 negative cells were nonreactive with OKM -1 (MAb which detects monocytes and 'null' lymphocytes) or with OKT11, 9.6, and 35.1, MAb against the T cell E receptor. Moreover ER +, T3 negative cells were not stained with OKT4, OKT8, OKT6, OKT9 , or OKT10 . Treatment of group II ER + cells with neuraminidase increased (from 27% to 74%) the mean percentages of T3 positive cells detected, but not other membrane antigens. ER + cells from group II patients, compared with normal and group I patients, exhibited diminished proliferative responses to PHA and Con-A (P less than 0.01) and supported poorly pokeweed mitogen-induced proliferation of normal allogeneic B cells (P less than 0.01). Thus, in approximately one-third of the CLL patients studied, many ER + cells poorly express a number of membrane antigens characteristic of normal mature T cells, one of which (T3) is unmasked by neuraminidase treatment. This phenotypic abnormality appears to be associated with significant T cell dysfunction in vitro and may, at least in part, contribute to the commonly encountered immunological defects present in these patients.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis*; D006801:Humans; D007945:Leukemia, Lymphoid / Q000276:immunology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008934:Mitogens / Q000494:pharmacology; D009439:Neuraminidase / Q000494:pharmacology; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D008934:Mitogens; D009439:Neuraminidase