Estudo do perfil funcional das células T de pacientes com Esclerose Múltipla e sua relação com o grau de incapacidade neurológica e resposta in vitro ao glicocorticoide

Abstract

The multiple sclerosis (MS) is a progressive autoimmune disease of central nervous system, having by targets the peptides of the oligodendrocytes proteins, cell responsible for the formation of the myelin sheath. Although studies about the immune events in MS patients during clinical relapses have demonstrated the involvement of Th17 cells in the immunopathogenesis, few data are available concerning the immune profile from these patients during remission phase. In this context, the objective of this study was evaluate functional aspects of T cells from remittent-recurrent MS (RR-MS) patients during the clinical remission and their relationship with neurological disabilities and the in vitro hidrocortisone (HC) response. Our results demonstrated that T cell proliferation induced by phytohemagglutinin (PHA) was lower in cell cultures from RR-MS patients, as compared with healthy individuals. The HC, however, was less potent in reducing T cell proliferation in cell cultures from RR-MS patients, as compared with control group. Among Th1 (IFN- γ and IL-2) and Th2 (IL-4 e IL-5) cytokines, only the production of IL-2 was significantly lower in cultures containing policlonally-activated T cells from patients. On the other hand, the production of Th17-related cytokines TNF-α, IL-6 and IL-17 was significantly higher in cell cultures from RR-MS patients, as compared with control group. Although higher IL-17 production in cell cultures from patients, no difference was observed with regard to anti-inflammatory cytokines production, IL-10 and TGF-β, between the two groups studied. Nevertheless, the addition of HC was less efficient in reducing IL-17 production by cell cultures from RR-MS patients. Finally, higher tendency in mounting Th17 response in patients was directly related to both higher LPS-induced in vitro IL-23 and IL-6 production by monocytes and higher in vivo LPS dosage. In summary, our results demonstrated that, even during clinical remission, Th17-related cytokines are dominant in T cells cultures of RR-MS patients, and this strong tendency should be related, at least in part, to higher sensibilization of innate immune cells by peripheral LPS and lower sensibility to inhibition to glucocorticoids.