Decreases in interleukin-4 secretion by invariant CD4-CD8-Vα24JαQ T cells in peripheral blood of patients with relapsing-remitting multiple sclerosis

The cytokine profile of invariant CD4(-)CD8(-)V alpha 24J alphaQ T cells from patients with multiple sclerosis (MS) was compared with that of healthy controls. CD4(-)CD8(-)V alpha 24(+) T cells from the peripheral blood of 12 patients with relapsing-remitting MS (RR-MS), 5 patients with progressive MS (CP-MS), and 9 control individuals were directly sorted into single wells and expanded in vitro for analysis of IL-4 and IFN-gamma secretion; 315 V alpha 24J alphaQ T cell clones were generated and their T cell receptor (TCR) sequenced. T cell functionality was determined by examining cytokine secretion upon TCR cross-linking. RR-MS patients exhibited lower frequencies of IL-4 secreting CD4(-)CD8(-)V alpha 24J alphaQ T cell clones than patients with CP-MS and controls. No differences in IFN-gamma secretion were observed between the groups. An IL-4 positive cytokine profile could be correlated to the cloning efficiency of the V alpha 24J alphaQ T cells. We conclude that alterations in cytokine secretion patterns of CD4(-)CD8(-)V alpha 24J alphaQ T cells may influence the immune system and thus contribute to relapsing-remitting MS. (C) 2000 Academic Press.