An OKT4+ T-Cell Population in Séezary Syndrome: Attempts to Elucidate Its Lack of Proliferative Capacity and Its Suppressive Effect

We have previously reported a case ot Sezary Syndrome (SS), in which an OKT4- T-cell population exhibited a defective response to non-specific mitogens, and an ability In 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 Sezary cells (SC) were essentially negative for activation activation (Ag) detected by monoclonal antibodies (MoAb) BI. 49.9. anti-Tac. OKT9. OKT10. and OKIal. After phytohaemagglutin (PHA) stimulation, all these Ag were expressed With the notable exception of OKT10. Further investigations of SC functions indicated that no inlerleukin 2 (IL.-2) biological activity was detected in culture supernalanls ot SC costimulated 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-indueed T -cell proliferation of normal PBMC Taken together, the data suggest that the target of suppressor activity is probably an important ohligarory intracellular event controlling DNA replication, which is common to both IL.-2-Independent and IL-2-dependent T-cell activation processes Human T-cell leukaemia/lymphoma virus I (HTLV-1) related p.19 and p.24 Ag were absent on fresh and.10-day cultured SC. suggesting the absence of HTI.V-1 infection, although not ruling out a proviral integration m the SC DNA.