FUNCTIONAL CAPACITY OF MEMORY CELLS CD8+ UNDER LYMPHOPENIA INDUCED BY INJECTION OF HYDROCORTISONE

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Abstract

Background. Wide use of glucocorticoids therapy for neoplasms, autoimmune diseases and allergies is associated with suppression of adaptive immunity that requires profound study of their immunoregulatory properties and immunotoxicity.

Results. In this work, using our model of selective activation of mouse CD8+ memory cells in the mixed lymphocyte reaction (MLR) in vitro, we show for the first time that intraperitoneal injection of high dose hydrocortisone (2.5 mg per animal) allows to detect memory cells in the thymus of animals immunized with allogeneic tumor cells. Similar to memory cells from other lymphoid organs, hydrocortisone-resistant thymic lymphocytes from immune animals respond on allogeneic stimulators subjected to severe heat shock and are immunologically specific to immunizing alloantigen. Thus, cortisone-resistant thymocytes are partially or completely represented by memory cells. We also show here that memory responses of heterozygotes on TCR a-chain knock-out (genetically incapable to secondary rearrangement of TCR achains) are significantly enhanced as compared with the ones of wild type mice.

Conclusion. These findings allows to suggest the hypothesis according to which memory T cell clones proliferating in primary immune response migrate into thymus providing necessary microenvironment for reexpression of recombinases. After editing of genes encoding TCR achains, such T lymphocytes can return to peripheral repertoire maintaining its wideness.

About the authors

D. B. Kazansky

Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Author for correspondence.
Email: kazansky1@yandex.ru

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

M. S. Vagida

Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

Yu. Yu. Silaeva

Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

A. A. Kalinina

Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

M. A. Zamkova

Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

L. M. Khromykh

Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

N. А. Persiyantseva

Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

L. Kh. Jolokhava

Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

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