Interferon-gamma and interleukin-4-producing T cells in peripheral blood of multiple sclerosis patients

Pro- and anti-inflammatory cytokines are thought to participate in the deve lopment and regulation of autoimmunity in multiple sclerosis (MS), a demyel inating disease of the central nervous system (CNS), We analysed the percen tage of interferon (IFN)-gamma and interleukin (IL)-4-producing cells in th e peripheral blood of both active and stable MS patients, and of healthy co ntrols. After short-term stimulation, cytokine-producing cells mere intrace llularly stained and sorted. Significantly lower percentages of IFN-gamma a nd IL-S-producing T cells mere found in stable MS patients than in controls , and in active than in stable patients. The diminution affected CD4(+) (Th 1, Th2) and CD8(+) (Tc1) phenotypes, Tc2 cells were not detected. The Th1/T h2 ratio did not differ in active and stable MS, nor in controls, The fact that Th2 and Tc1 cell percentages mere higher in stable than in active RIS possibly indicates that these cells play a downmodulating role in the immun e response. In contrast, a role in exacerbating the immune response is not attributable to Th1 cells, given their reduction in acute MS. Our data do n ot support the hypothesis that MS is a Th1/Th2 paradigmatic disease; rather , they suggest that sequestration in the CNS, or activation-induced apoptos is (whether in vivo or irt vitro) may explain reduced levels of IFN-gamma a nd IL-4-producing subsets in the peripheral blood of clinically acute patie nts.