The expression and function of CD3 and CD5 in patients with primary Sjögren's syndrome

We studied the expression and function of 2 cell surface markers that induce T cell activation, CD3 and CD5, in 19 patients with primary Sjögren's syndrome (SS). The expression of CD3+ lymphocytes was normal, but CD3 function was moderately reduced, as measured by anti-CD3-induced T cell proliferation. Anti-CD3-induced stimulation of T cell help for Ig production and non-major histocompatibility complex-restricted (natural) killing were normal. In contrast, there was reduced expression and function of the CD5 molecule on peripheral blood lymphocytes of the SS patients. The ratio of CD5+ to CD3+ lymphocytes was 0.45 in SS patients compared with 0.85 in normal subjects, indicating that the CD3+ cells are relatively CD5-deficient in SS patients. Anti-CD5 monoclonal antibody did not augment suboptimal anti-CD3 stimulation of whole peripheral blood lymphocytes or of purified T lymphocytes from SS patients, which indicated impaired functioning of the CD5 molecule. A significant impairment in proliferation was found in response to phorbol myristate acetate and to ionomycin in combination, suggesting defective intracellular signaling. Findings from serial studies of individual patients suggested that normal or low expression of CD5 on T cells can be stable over periods as long as 2 years. However, in 2 patients who required systemic therapy, a correction of the CD5 lymphocyte abnormality occurred in association with clinical remission, which suggests the potential reversibility of this condition. Our findings suggest a possible defect in intracellular signaling in primary SS, related in part to the CD5 molecule, which may provide a molecular explanation for the T cell hyporesponsiveness that is characteristic of this disease.