Cytotoxic activity of CD4 T Cells during the early stage of autoimmune neuroinflammation
Farias, A. S.; Pradella, F.; Boldrini, V. O.; Marques, A. M.; Morais, G. D.; Francelin, C.; Cocenza, R. S.; Lima, V. C.; Bonora-Jr, M.; Brunetti, N. S.; Campos, B. B.; Fonseca, E. S. M.; Rocha-Parise, M.; Stella, C. R. V.; Damasceno, A.; von Glehn, F.; Longhini, A. L.; Santos, L. M. B.
Show abstract
Pathogenic CD4+ T cells are capable of initiating neuroinflammation in experimental autoimmune encephalomyelitis (EAE). However, the precise effector mechanism of these autoaggressive CD4+ T cells is not entirely elucidated. Here, we demonstrated that pathogenic CD4+ T cells, upon autoantigen stimulation, developed a cytotoxic phenotype at the onset of EAE. The cytotoxic activity of pathogenic CD4+ T cells was sufficient to explain the initial myelin lesion. Consistently, CD4+ T cells of peripheral blood (PBMCs) and cerebrospinal fluid (CSF) from relapse-remitting multiple sclerosis (RRMS) patients present an enhancement of the cytotoxic profile in comparison with healthy control (HC). Moreover, cytotoxic CD4+ T cells (CD4-CTLs) are restrained in the PBMCs of Natalizumab-treated RRMS patients. Mechanistically, autoaggressive CD4-CTLs matched the majority of the molecular pathways of effector CD8+ T cells. Altogether, our findings point to potential new targets for monitoring MS diagnosis, treatment, and the development of novel therapeutic avenues.
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