ABNORMALITIES IN CD69 EXPRESSION, CYTOSOLIC PH AND CA2-ERYTHEMATOSUS(DURING ACTIVATION OF LYMPHOCYTES FROM PATIENTS WITH SYSTEMIC LUPUS)

Several immune-regulatory abnormalities have been described in SLE pat ients. T cell dysfunction in SLE includes defective in vitro prolifera tive responses to several stimuli, reduced IL-2 production and a poor helper function. It has been widely proposed that this defective T cel l immunoregulatory function has a key role in the hyperactivity of B c ells and auto-antibody production in SLE. However, it has not been elu cidated whether or not this cell dysfunction is intrinsic to lymphocyt es or is due to other factors such as anti-lymphocyte auto-antibodies. In this study we have evaluated some important early cell activation events in T and non-T lymphocytes from patients with systemic lupus er ythematosus (SLE). Peripheral blood lymphocytes from SLE patients and controls were isolated. The intracellular pH (pH(i)), cytosolic calciu m (Ca-i(2+)) and CD69 expression were determined by spectrofluorometry and flow cytometry. Modifications of these parameters in response to protein kinase C (PKC) activators, mitogenic lectins and calcium ionop hores were also studied We found a significant reduction in the increa se of pH(i) in response to PKC activators (PMA) in SLE cells. In addit ion, the induction of CD69 expression by PMA was significantly lower i n T cells from SLE patients. By contrast, freshly isolated non-stimula ted SLE cells exhibited a significantly higher pH(i), as well as an in creased baseline expression of the early cell activation antigen CD69. On the other hand, the increase in Ca-i(2+) in response to a Ca2+ ion ophore (4Br-A23187) or thapsigargin in Ca2+-free solutions, was smalle r in SLE lymphocytes. We concluded that T cells from SLE patients exhi bit abnormalities in several key early cell activation events (pH(i), Ca-i(2+) and CD69 expression). These abnormalities could have an impor tant role in the T cell dysfunction observed in SLE. The presence of T cells with a preactivated phenotype in the peripheral blood of SLE pa tients, could be a reflection of the ongoing autoimmune phenomena that is occurring in these patients.