PERIPHERAL-BLOOD LYMPHOCYTES IN SLE - HYPEREXPRESSION OF CD154 ON T-LYMPHOCYTES AND B-LYMPHOCYTES AND INCREASED NUMBER OF DOUBLE-NEGATIVE T-CELLS

Abnormalities in the regulation of both cell-mediated and humoral immu nity have been implicated in the pathophysiology of systemic lupus ery thematosus (SLE). Cognate contact;dependent T-B cell interactions invo lving CD154 (CD40 ligand) on activated T cells and CD40 on B lymphocyt es have a critical role in antibody production Abnormal CD154 expressi on on lymphocytes may play a role in the production of potentially pat hogenic autoantibodies and defects in self-tolerance mechanisms may be important. Failure of intrathymic or peripheral deletion of autoreact ive T cells may also result in an autoimmune phenotype. Elevated level s of CD3(+)CD4(-)/8(-) (double negative) T cells (DNT) in the peripher al blood are a surrogate marker for defects of this type. The expressi on csf CD154 on T and B cells was evaluated and levels of double negat ive T cells in the peripheral blood were assessed by two and three col our now cytometric analyses. We studied peripheral blood lymphocytes i n 48 patients with SLE. Twenty-five normal subjects and 12 patients wi th rheumatoid arthritis (RA) were studied as disease controls. T cells in 22/48 (45%) lupus patients expressed CD154 between 20-80% (median= 52%). In normal controls and RA patients 8-18% T cells were CD154(+). Twelve patients (30%) had elevated expression of CD154 (20-50%) on B c ells. In the control RA patients, less than 15% T cells were CD154(+). Twelve of 48 SLE patients had elevated numbers of DNT cells (18-27%). The control subjects had DNT cell numbers <10. These observations sug gest that defects in either the intrathymic or peripheral deletion cif potentially pathogenic T lymphocytes may play a role in the pathogene sis of SLE. The high expression of CD154 on both T and B cells may als o be important in mediating the production of potentially harmful auto antibodies. (C) 1998 Academic Press