Type 1 and type 2 cytokine-producing CD4+ and CD8+ T cells in primary antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune condition characterized by thrombosis and/or recurrent fetal loss as well as the presence of autoantibodies against epitopes present on phospholipid-binding proteins. The role of cellular immunity in the pathogenesis of the syndrome remains unclear. We studied the cellular phenotype and the production of type 1 [interferon (IFN)-gamma, interleukin (IL)-2] and type 2 (IL-4, IL-10) cytokines by CD4+ and CD8+ T-lymphocyte subsets in 13 patients with untreated primary APS (PAPS) and in 32 healthy controls. The production of cytokines was determined in T cells after a 5-h culture with or without mitogenic stimulation using a flow cytometric method of intracellular cytokine staining. In six of the patients these studies were repeated 6 months later. In PAPS patients we found a reduced percentage of circulating CD4+CD45RA+ and an increased percentage and absolute number of CD8+HLA-DR+ cells. A type 1 response was observed in the patients' unstimulated cells, indicated by an increase in IFN-gamma-producing CD8+, IL-2-producing CD4+ T cells, and a decrease in IL-4-producing CD4+ and CD8+ T cells. Similar results were obtained in the patients at follow-up. Taken together, these results suggest a chronic in vivo stimulation of CD4+ and CD8+ T cells in PAPS patients exhibiting a type 1 polarization. Changes of cellular immunity may contribute to the pathogenesis of the clinical manifestations of the syndrome and might be proven to be useful targets for therapeutic interventions in the future.