Differences in systemic and central nervous system cellular immunity relevant to relapsing-remitting multiple sclerosis

In order to elucidate the differences between systemic and central nervous system (CNS) immunity that are relevant to exacerbations of multiple sclerosis ( MS), paired peripheral blood and cerebrospinal fluid (CSF) samples obtained from 36 non-treated patients with relapsing-remitting MS (RRMS) were simultaneously examined using flow cytometry to determine the percentages of functional lymphocyte subsets, as well as enzyme-linked immunosorbent assays for measuring soluble immune mediators. Active RRMS patients (n = 27) were characterized by an increase in CD4(+) CXCR3(+) Th1 cells in blood as compared with inactive patients (n = 9), and this parameter was inversely correlated with plasma levels of IL-10 and IL-12p70. In contrast, an increase in the percentage of CD4(+)CD25(+) cells and a decrease in the percentage of CD8(+) CD11a(high) cells were features of CSF samples from those with active RRMS. Further, CSF CD4(+) CD25(+) cells had a close association with leukocyte counts as well as albumin and CXCL10 levels in the CSF, and, thus, could be useful as a measure for inflammatory reactions in the CNS. On the other hand, CD8(+)CD11a(high) cells may function as immunoregulatory cells, as their percentage in the CSF showed a positive correlation with CSF levels of the anti-inflammatory cytokine IL-4. These findings suggest that MS relapses occur in a combination with altered cell-mediated immunity that differs between the peripheral blood and CSF compartments, while measurement of lymphocyte subsets may be helpful for monitoring disease status.