Cytotoxic T cell subsets in peripheral blood and cerebrospinal fluid from patients with multiple sclerosis

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Abstract

Using multicolor flow cytometry, the main cytotoxic T lymphocytes (Tcyt) subsets were identified, based on the expression of CD45RA and CD62L in paired samples of peripheral blood and cerebrospinal fluid from the patients during the relapse (n = 32) and remission (n = 20) of multiple sclerosis (MS), as well as in the peripheral blood samples of healthy volunteers (n = 51). During the relapse of MS, we have observed a decreased relative number of CD3+CD4+ cells and CD4/CD8 ratio in cerebrospinal liquor. In peripheral blood taken from the relapsed MS patients, we have found significant correlations between EDSS score and absolute counts (r = -0,430, p = 0.014), and with relative numbers of CD45RA+CD62L+Tcyt (r = -0,502, p = 0.003). In remission state of MS, the relative numbers of blood CD45RA-CD62L-Tcyt cells exhibited a significant decrease (p = 0.005) to 8.70% (6.51-11.63) against control group with 12.18% (10.38-15.24), although it did not significantly differ (p = 0.114) from the relapsed patients with 11.31% (8.28-13.90). Studies of liquor samples have shown that, during MS relapse, the percentage of CD45RA-CD62L-Tcyt was increased (p = 0.027) up to 8.16% (6.40-11.40), while in remission state these cells comprised only 6.49% (4.51-8.39) from the total CD3+ cell number. During relapse of MS, some positive correlations were revealed between the relative number of “naïve”, CM, EM and TEMRA Tcyt from liquor, and the percentages, as well as contents of similar T cell subsets in peripheral blood samples. The inverse relationship between the level of EM Tcyt from liquor and peripheral blood “naive” cells showed the close relationship between these two Tcyt subsets and clinical manifestations of MS (i.e., scores of EDSS scale). During the remission period, most of these correlations are disrupted. Further investigations of cytotoxic T cells dynamics in peripheral blood and cerebrospinal fluid will help to approach the understanding of MS pathogenesis by revealing novel markers for the clinical prognosis in this disorder.

About the authors

MariIa K. Serebriakova

Institute of Experimental Medicine

Author for correspondence.
Email: m-serebryakova@yandex.ru
ORCID iD: 0000-0003-2596-4220

Research Associate, Laboratory of Cellular Immunology, Department of Immunology, Institute of Experimental Medicine, St. Petersburg, Russian Federation

Russian Federation, St. Petersburg

Alexander G. Ilves

N. Bechtereva Institute of Human Brain

Email: ailves@hotmail.com

PhD (Medicine), Senior Research Associate, Laboratory of Targeted Intracerebral Drug Delivery, N. Bechtereva Institute of Human Brain, St. Petersburg, Russian Federation

Russian Federation, St. Petersburg

Valeriy M. Lebedev

N. Bechtereva Institute of Human Brain

Email: lebedevvaleriy@bk.ru

Junior Research Associate, Laboratory of Targeted Intracerebral Drug Delivery, N. Bechtereva Institute of Human Brain, St. Petersburg, Russian Federation

Russian Federation, St. Petersburg

Olga M. Novoselova

N. Bechtereva Institute of Human Brain

Email: dr.novoselova@gmail.com

Junior Research Associate, Laboratory of Targeted Intracerebral Drug Delivery, N. Bechtereva Institute of Human Brain, St. Petersburg, Russian Federation

Russian Federation, St. Petersburg

Lidia N. Prakhova

N. Bechtereva Institute of Human Brain

Email: l.n.prakhova@hotmail.com

PhD, MD (Medicine), Head, Laboratory of Targeted Intracerebral Drug Delivery, N. Bechtereva Institute of Human Brain, St. Petersburg, Russian Federation

Russian Federation, St. Petersburg

Igor V. Kudryavtsev

Institute of Experimental Medicine; Far Eastern Federal University; First St. Petersburg State I. Pavlov Medical University

Email: igorek1981@yandex.ru

PhD (Biology), Head, Laboratory of Cellular Immunology, Department of Immunology, Institute of Experimental Medicine, St. Petersburg; Senior Research Associate, Far Eastern Federal University, Vladivostok; Associate Professor, Department of Immunology, First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation

Russian Federation, St. Petersburg; Vladivostok; St. Petersburg

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Supplementary files

Supplementary Files
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1. JATS XML
2. Figure 1. Gating strategy of flow cytometric analysis of main peripheral blood (upper row of histograms) and liquor (lower row of histograms) CD8+ T cell subsets

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3. Figure 2. Frequencies of main maturation CD8+T cell subsets in peripheral blood and liquor from patients with multiply sclerosis during relapse (n = 32, upper row) and remission (n = 20, lower row) periods of disease

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Copyright (c) 2023 Serebriakova M.K., Ilves A.G., Lebedev V.M., Novoselova O.M., Prakhova L.N., Kudryavtsev I.V.

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