Decreases in interleukin-4 secretion by invariant CD4(-)CD8(-)V alpha 24J alpha Q 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 fr om 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 well s 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 (T CR) sequenced. T cell functionality was determined by examining cytokine se cretion upon TCR cross-linking. RR-MS patients exhibited lower frequencies of IL-4 secreting CD4(-)CD8(-)V alpha 24J alphaQ T cell clones than patient s with CP-MS and controls. No differences in IFN-gamma secretion were obser ved between the groups. An IL-4 positive cytokine profile could be correlat ed 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 rela psing-remitting MS. (C) 2000 Academic Press.