T-LYMPHOCYTES FROM AUTOIMMUNE THROMBOCYTOPENIC PURPURA SHOW A DEFECTIVE ACTIVATION AND PROLIFERATION AFTER CYTOPLASMIC MEMBRANE AND INTRACYTOPLASMIC MITOGENIC SIGNALS

T lymphocyte activation and proliferation are complex cellular process es involving membrane and cytoplasmatic molecules as well as the secre tion and response to cytokines, mainly interleukin 2. There is increas ing evidence that autoimmune thrombocytopenic purpura (ATP) is associa ted with an alteration of the regulation of the immune system. The bla stogenic response of purified T lymphocytes to mitogens that interact with membrane molecules (phytohemaglutinin, anti-CD3 monoclonal antibo dy) and with intracytoplasmic protein kinase C (phorbol myristate acet ate) has been investigated in 22 ATP patients and 18 healthy controls. After the signal given by the three different mitogens H-3!-thymidin e uptake in T lymphocytes from ATP patients was found to be significan tly decreased with respect to that found in healthy controls under sim ilar experimental conditions (P < 0.05). Analysis of the cell cycle pr ogression in these T lymphocytes from ATP patients, showed a significa ntly diminished percentage of cells in S-phase after PHA stimulation ( P < 0.05). The percentage of CD3+ cells in the CD2+ lymphocyte prepara tions was significantly decreased in ATP patients relative to healthy controls (P < 0.05). But there was no significant correlation between this percentage and the blastogenic response to PHA in the CD2+ cellul ar preparations from both groups of subjects. No significant differenc es were found in the percentages of CD4+ and CD8+ cells. These data in dicate that the impaired blastogenic response of T lymphocytes from AT P patients may be ascribed to an intrinsic defect in these T cells. Th is defective proliferative response of T lymphocytes from ATP patients cannot be ascribed to either defective interleukin 2 production or re ceptor expression which were both similar to those of healthy controls (P > 0.05). And, the presence of saturating amounts of exogenous inte rleukin 2 did not normalize the defective proliferative response the m itogenic signals on the part of T lymphocytes from ATP patients. We co nclude that T lymphocytes from ATP patients have a defective prolifera tive response to membrane and intracytoplasmatic mitogenic signals. (C ) 1993 Wiley-Liss, Inc.