PERIPHERAL BLOOD CCR6+CXCR3– CD8+ T CELLS IN THE PATHOGENESIS OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

Abstract

Introduction. Multiple sclerosis (MS) is a chronic progressive neurodegenerative autoimmune disease, that is characterized by the presence of disseminated patches of demyelination in the brain and spinal cord, containing different subsets of immune cells, including CD8+ T cells. Currently, CD8+ T cells can be subdivided into three main subsets, including Tc1, Tc2 and Tc17 according to their cytokine production profile and phenotype. A balance between the cytolytic Tc1, on the one hand, and cytokine-producing Tc2 and Tc17 cell subsets, on the other hand, seems to play crucial role in emergence of diverse pathological conditions including autoimmunity. Thus, we have examined the frequency of Tc cell subsets in peripheral blood of patients with relapsing-remitting MS (MS, n=25) and sex and age matched healthy individuals (HC, n=24). Methods. To analyze the frequency of CD8+ T cell subsets we used multicolor flow cytometry. We evaluated the relative and absolute frequencies of Tc1 (CCR6–CXCR3+), Tc2 (CCR6–CXCR3–), Tc17 (CCR6+CXCR3–) and Tc17.1 (CCR6+CXCR3+) cells, as well as we measured the relative frequencies of mentioned subsets within main maturation stages of CD8+ T cell, including «naïve» (CD45RA+CD62L+), central (СМ) and effector (ЕМ) memory, and TEMRA (CD45RA+CD62L–) cells. Results. First, we noticed that the relative frequency of Tc1 was decreased in MS group vs HC, while the relative and absolute frequencies of Тс17 of Тс17.1 were significantly elevated during MS. Next, our data revealed a significant increase in the frequencies of Тс17 on all analyzed stages of CD8+ T cell maturation, that were identified in peripheral blood samples from MS patients. Furthermore, the differences with the control group were most critical in the case of ЕМ and TEMRA CD8+ T cell subsets (11,66% (4,75; 14,69) vs 2,45% (1,48; 3,89), and 4,91% (3,68; 8,63) vs 0,41% (0,11; 1,30), respectively, with р<0,001 in both cases), exhibited enhanced migratory properties to the inflammatory sites. Conclusions. Thus, we provide some new insights in the frequency of ‘polarized’ CD8+ T cell subsets in patients with MS, and the obtained data point to an important part of Tc17 cell in the pathogenesis of MS, and can be used for development of new diagnostic techniques and treatment approaches for MS.