An OKT4+ T-cell population in Sézary syndrome: attempts to elucidate its lack of proliferative capacity and its suppressive effect.
We have previously reported a case of Sézary Syndrome (SS), in which an OKT4+ T-cell population exhibited a defective response to non-specific mitogens, and an ability to suppress lectin-induced T-cell proliferation and pokeweed mitogen (PWM)-induced B-cell differentiation of normal donor peripheral blood mononuclear cells (PBMC). We report now that resting Sézary cells (SC) were essentially negative for activation antigens (Ag) detected by monoclonal antibodies (MoAb) B1.49.9, anti-Tac, OKT9, OKT10, and OKIa1. After phytohaemagglutin (PHA) stimulation, all these Ag were expressed with the notable exception of OKT10. Further investigations of SC functions indicated that no interleukin 2 (IL-2) biological activity was detected in culture supernatants of SC constimulated with PHA and phorbol myristate acetate (PMA). Interestingly, such stimulated SC exhibited a marked capacity to absorb exogenous IL-2 while remaining unable to proliferate. These data suggest that patient's unresponsiveness to PHA may be unrelated to IL-2 as an extracellular growth signal, but may instead be due to a failure in a later cellular activation event, subsequent to the binding of IL-2 to its receptors. Lack of T10 Ag expression may be involved as a cause or a consequence. Kinetic study of suppression of PHA-induced T-cell proliferation of normal PBMC revealed that inhibition occurred during the first 24 h; moreover we showed that it was not due to limitation of available IL-2 since it persisted in excess of IL-2; remarkably the growth of an IL-2-dependent murine cell line was unaffected by the presence of SC. Further, inhibition was also observed on IL-2-independent calcium ionophore A 23187-induced T-cell proliferation of normal PBMC. Taken together, the data suggest that the target of suppressor activity is probably an important obligatory intracellular event controlling DNA replication, which is common to both IL-2-dependent and IL-2-independent T-cell activation processes. Human T-cell leukaemia/lymphoma virus I (HTLV-I) related p.19 and p.24 Ag were absent on fresh and 30-day cultured SC, suggesting the absence of HTLV-I infection, although not ruling out a proviral integration in the SC DNA.
D000328:Adult; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D007399:Interphase; D007700:Kinetics; D008213:Lymphocyte Activation; D010641:Phenotype; D010835:Phytohemagglutinins / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D012751:Sezary Syndrome / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7