Peripheral blood CCR6<sup>+</sup>CXCR3<sup>-</sup>CD8<sup>+</sup>T cells in pathogenesis of relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is a chronic progressive neurodegenerative autoimmune disease characterized by disseminated demyelination patches in brain and spinal cord, containing different subsets of immune cells, including CD8+T cells. Currently, CD8+T cells may 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 and cytokine-producing Tc2 and Tc17 cell subsets 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 healthy individuals (HC, n = 24) matched for sex and age. 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, like as their relative distribution along the main maturation stages of CD8+T cells, including ‘‘naïve’’ (CD45RA+CD62L+), central (СМ) and effector (ЕМ) memory, as well as TEMRA (CD45RA+CD62L-) cells. First, we have found that the relative frequency of Tc1 was decreased in MS group versus HC, whereas the relative and absolute frequencies of Тс17 of Тс17.1 were significantly elevated in MS patients. Next, our data revealed a significantly increased frequency of Тс17 cells at all analyzed stages of CD8+T cell maturation in peripheral blood samples from MS patients. Moreover, the differences against control group were more pronounced in the ЕМ and TEMRA CD8+T cell subsets which are able to migrate to inflammation sites (11.66% (4.75-14.69) versus 2.45% (1.48-3.89) and 4.91% (3.68-8.63) versus 0.41% (0.11-1.30), respectively, р 0.001 in both cases). Hence, we provide some new insights in the frequency of ‘‘polarized’’ CD8+T cell subsets in patients with MS. The obtained data suggest Tc17 cells to be an important part in MS pathogenesis which may be used for development of new diagnostic techniques and treatment approaches in MS patients.