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

https://doi.org/10.17650/2313-805X-2017-4-4-42-48

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
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



M. S. Vagida
Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



Yu. Yu. Silaeva
Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



A. A. Kalinina
Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



M. A. Zamkova
Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



L. M. Khromykh
Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



N. А. Persiyantseva
Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



L. Kh. Jolokhava
Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



References

1. Казанский Д.Б., Петрищев В.Н., Штиль А.А. и др. Использование теплового шока антигенпрезентирующих клеток для функционального тестирования аллоспецифических Т-клеток памяти. Биоорганическая химия 1999;25(2):117–28. [Kazanskiĭ D.B., PetrishchevV.N., Shtil’ A. A. etal. Use of heat shock of antigen-presenting cells for functional testing of allospecificity memory T-cells. Bioorganicheskaya khimiya = Bioorganic Chemistry 1999;25 (2):117–28. (In Russ.)].

2. Казанский Д.Б., Чернышева А.Д., Сернова Н.В. и др. Природа эпитопов, распознаваемых Т-лимфоцитами в аллогенном иммунном ответе. Молекулярная биология 1998;32(4):692–702. [Kazanskiĭ D.B., ChernyshevaA.D., SernovaN.V. etal. The nature of epitopes, recognized by T-lymphocytes in the allogenic immune response. Molekulyarnaya biologiya = Molecular Biology 1998;32(4):692–702. (In Russ.)].

3. Побезинская Е.Л., Побезинский Л.А., Силаева Ю.Ю. и др. Кросс-реактивность Т-клеточного рецептора клона клеток памяти CD8+, полученного в ответе на иммунизацию клетками аллогенной опухоли. Бюллетень экспериментальной биологии и медицины 2004;137(5):493–8. [PobezinskayaE.L., PobezinskiiL.A., SilaevaY.Y. etal. Cross reactivity of T cell receptor on memory CD8+ cells isolated after immunization with allogeneic tumor cells. Bulleten’ experimental’noy biologii i meditsiny = Bulletin of Experimental Biology and Medicine 2004;137(5):493–8. (In Russ..)].

4. Гриненко Т.С., Побезинская Е.Л., Побезинский Л.А. и др. Подавление клетками памяти CD8+ первичного аллогенного ответа. Бюллетень экспериментальной биологии и медицины 2005;140(5):545–9. [GrinenkoT.S., PobezinskayaE.L., PobezinskiiL.A. etal. Suppression of primary allogenic response by CD8+ memory cells. Bulleten’ experimental’noy biologii i meditsiny = Bulletin of Experimental Biology and Medicine 2005;140(5):545–9. (InRuss.)].

5. Звездова Е.С., Гриненко Т.С., Побезинская Е.Л. и др. Корецепторная функция CD4 в ответе на молекулу MHC класса I. Молекулярная биология 2008;42(4):662–72. [ZvezdovaE.S., GrinenkoT.S., PobezinskaiaE.L. etal. Coreceptor function of CD4 in response to MHC class I molecule. Molekulyarnaya biologiya = Molecular Biology 2008;42(4):662–72. (In Russ.)].

6. Звездова Е.С., Силаева Ю.Ю., Вагида М.С. и др. Создание трансгенных животных, экспрессирующих αиβ-цепи аутореактивного TCR. Молекулярная биология 2010;44(2):311–22. [ZvezdovaE.S., SilaevaIu.Iu., Vagida M.S. et al. Generation of transgenic animals, expressing alphaand beta-chains of autoreactive TCR. Molekulyarnaya biologiya = Molecular Biology 2010;44 (2):311–22. (In Russ.)].

7. Силаева Ю.Ю., Калинина А.А., Вагида М.С. и др. Сокращение пула Т-лимфоцитов с поверхностным фенотипом эффекторов и клеток памяти под воздействием экспрессии трансгена β-цепи Т-клеточного рецептора. Биохимия 2013;78(5):714–26. [SilaevaYu.Yu., KalininaA.A., Vagida M.S. et al. Decrease in pool of T lymphocytes with surface phenotypes of effector and central memory cells under influence of TCR transgenic β-chain expression. Biokhimiya = Biochemistry 2013;78(5):714–26. (In Russ.)].

8. Silaeva Yu.Yu., Grinenko T.S., Vagida M.S. et al. Immune selection of tumor cells in TCR β-chain transgenic mice. JImmunotoxicol 2014;1(4):393–9.

9. Казанский Д.Б., Силаева Ю.Ю., Калинина А.А. и др. Трансплантационный и специфический противоопухолевый иммунитет в ретроспективе: новые модели, основанные на трансгенезе цепей Т-клеточного рецептора. Успехи молекулярной онкологии 2016;3(1):14–27. [Kazanskiy D.B., Silaeva Yu.Yu., Kalinina A.A. Transplantational and specific antitumor immunity in retrospective view: new models based on transgenesis of individual chains of T-cell receptor. Uspekhi molekulyarnoy onkologii = Advances in Molecular Oncology 2016;3(1):14–27. (In Russ.)].

10. Sukumar M., Kishton R.J., Restifo N.P. Metabolic reprograming of anti-tumor immunity. CurrOpinImmunol 2017;46:14–22.

11. Казанский Д.Б., Силаева Ю.Ю., Калинина А.А. и др. Метаболические аспекты адоптивной иммунотерапии опухолей. Успехи молекулярной онкологии 2017;4(3):21–6. [KazanskiyD.B., SilaevaYu.Yu., KalininaA.A. Metabolic aspects of adoptive immunotherapy of tumors. Uspekhi molekulyarnoy onkologii = Advances in Molecular Oncology 2017;4(3):21–6. (In Russ.)].

12. Craddock C.G. Corticosteroid-induced lymphopenia, immunosuppression, and body defense. Ann Intern Med 1978;88(4):564–6.

13. Anfalova T.V., Khromykh L.M., Petrishchev V.N. et al. Characteristics of the cells producing thymic chemotactic factor for bone marrow stem cells. Ontogenez 2002;33(2):90–4.

14. Sprent J., Surh C.D. Re-entry of mature T cells to the thymus: an epiphenomenon? Immunol Cell Biol 2009;87(1):46–9.

15. King C.C., Jamieson B.D., Reddy K. et al. Viral infection of the thymus. J Virol 1992;66(5):3155–60.

16. Yehuda A.B., Friedman G., Wirtheim E. et al. Checkpoints in thymocytopoiesis in aging: expression of the recombination activating genes RAG-1 and RAG-2. Mech Ageing Dev 1998;102(2–3): 239–47.

17. Higdon L.E., Deets K.A., Friesen T.J. et al. Receptor revision in CD4 T cells is influenced by follicular helper T cell formation and germinal-center interactions. Proc Natl Acad Sci USA 2014;111(15):5652–7.


Review

For citations:


Kazansky D.B., Vagida M.S., Silaeva Yu.Yu., Kalinina A.A., Zamkova M.A., Khromykh L.M., Persiyantseva N.А., Jolokhava L.Kh. FUNCTIONAL CAPACITY OF MEMORY CELLS CD8+ UNDER LYMPHOPENIA INDUCED BY INJECTION OF HYDROCORTISONE. Advances in Molecular Oncology. 2017;4(4):42-48. (In Russ.) https://doi.org/10.17650/2313-805X-2017-4-4-42-48

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ISSN 2313-805X (Print)
ISSN 2413-3787 (Online)