Longitudinal analysis of IL-17 and/or IL-22 producing CD4+ T lymphocytes in relapsing remitting multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. We have shown that while T helper (Th)17 cells were barely detectable in the peripheral blood (PBMC) from healthy subjects and patients with inactive MS, they were increased strikingly in patients with clinical signs of an MS exacerbation. Longitudinal analysis showed that the increase in Th17 cells was always associated with the shift from inactive to active disease in relapsing-remitting (RR) MS. In this study, we focused our attention on IL-22, a pro-inflammatory cytokine related to Th17, that might play a critical role in promoting the Th17-dependent lymphocyte invasion of the central nervous system by binding specific receptors on brain blood barrier epithelial cells. We quantified the frequency of ex vivo CD4+IL-17-, IL-22- and IFNgamma-producing T cells in PBMC and in some cerebrospinal fluid (CSF) of untreated patients affected by RRMS that undergone periodical blood withdrawals for immunological samples. In the PBMC we found an increased number of IL-17-producing CD4+ cells that co-secrete IL-22 in AMS patients. These Th17 cells were MBP-specific, suggesting a pathogenetic role of these cells in the disease. Moreover, a distinct subset of IL-22-producing CD4+ cells, generally ranged between 3% and 10% was present in the longitudinal study independent of disease status, as well as IFNgamma-secreting CD4+ T cells. In the CSF, an expansion of IL-17-producing CD4+ cells that co-secrete IL-22 was detected too. Moreover,we found an enrichment of IFNgamma-producing CD4+ cells and surprisingly of CD4+ cells producing IL-22 alone. These data indicates that in MS there are 3 distinct population: the IFNgamma-producing cells, the Th17 that co-produce IL-22 and the IL-22 producing CD4+ T cells. Further study are currently undergoing to clarify their role in MS exacerbation.