In vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions

IL-7 is a key factor for the survival and maintenance of CD4+ central (Tcm) and effector (Tem) memory cells in the whole body. In many autoimmune diseases, an elevated level of IL-7 is detected in blood serum and at the site of inflammation, thus suggesting participation of this homeostatic factor i...

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Autores principales:	E. A. Blinova, A. V. Kolerova, V. E. Balyasnikov, V. A. Kozlov
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2020
Materias:	central memory t cells effector memory t cells il-7 il-7 receptor cd5 proinflammatory cytokines inflammation model in vitro Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/e294256b11304047b945494ee99db0db
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spelling	oai:doaj.org-article:e294256b11304047b945494ee99db0db2021-11-18T08:03:50ZIn vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions1563-06252313-741X10.15789/1563-0625-IVM-1975https://doaj.org/article/e294256b11304047b945494ee99db0db2020-12-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1975https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XIL-7 is a key factor for the survival and maintenance of CD4+ central (Tcm) and effector (Tem) memory cells in the whole body. In many autoimmune diseases, an elevated level of IL-7 is detected in blood serum and at the site of inflammation, thus suggesting participation of this homeostatic factor in the survival of memory T cells, including auto-reactive clones, in inflammatory disorders. The aim of the study was to investigate the mechanisms of maintaining CD4+ memory T cells under normal and inflammatory conditions. We developed an in vitro model of inflammation, based on induction of pro-inflammatory cytokines, and then evaluated the effects of IL-7 upon purified sorted populations of CD4+Tcm and Tem under normal conditions and in vitro inflammatory model. IL-7 treatment promoted maintenance of CD4+Tcm phenotype in all variants of cultures. In the absence of contact with adherent cell fraction, the IL-7-induced proliferation of Tcm and Tem was slightly reduced, both under normal and inflammatory conditions, thus suggesting low sensitivity of memory T cells to contacts with MHC, and, probably, a requirement for additional signals to provide complete stimulation with IL-7. The last suggestion is also supported by data about CD127 and CD132 expression, i.e., in the absence of contact with MHC, the proportion of CD127+CD132+ cells was decreased in both subpopulations of CD4+ memory cells. Upon in vitro cultures, IL-7 contributed to decreased expression of CD127, and increased expression of CD132 on CD4+Tcm and Tem. We have evaluated the CD4+Tcm and Tem populations by affinity of T cell receptor (TCR), using the level of CD5 expression. Т cells with high TCR affinity for self-antigens are known to have higher expression of CD5. In comparison to Tem, the Tcm contained more CD5high cells. In cultures, IL-7 promoted a high level of CD5 expression on Tcm, which was comparable to levels observed in peripheral blood cells. High CD5 expression on Tem was observed after stimulation with IL-7 in the in vitro inflammatory model. In the absence of contact with MHC, the number of CD5high cells decreased among CD4+Tem and Tcm. Thus, CD4+Tcm cells with high affinity for autologous antigens are probably dependent on the presence of homeostatic factors, in particular, IL-7, and contacts with antigen-presenting cells (APCs). Under conditions of inflammation, no changes were revealed in the mechanism of maintaining CD4+Tcm, in contrast to CD4+Tem. Being less dependent on IL-7 under normal conditions, CD4+CD5highTem are accumulated in the presence of IL-7 under in vitro inflammatory conditions.E. A. BlinovaA. V. KolerovaV. E. BalyasnikovV. A. KozlovSPb RAACIarticlecentral memory t cellseffector memory t cellsil-7il-7 receptorcd5proinflammatory cytokinesinflammation model in vitroImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 22, Iss 5, Pp 837-846 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	central memory t cells effector memory t cells il-7 il-7 receptor cd5 proinflammatory cytokines inflammation model in vitro Immunologic diseases. Allergy RC581-607
spellingShingle	central memory t cells effector memory t cells il-7 il-7 receptor cd5 proinflammatory cytokines inflammation model in vitro Immunologic diseases. Allergy RC581-607 E. A. Blinova A. V. Kolerova V. E. Balyasnikov V. A. Kozlov In vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions
description	IL-7 is a key factor for the survival and maintenance of CD4+ central (Tcm) and effector (Tem) memory cells in the whole body. In many autoimmune diseases, an elevated level of IL-7 is detected in blood serum and at the site of inflammation, thus suggesting participation of this homeostatic factor in the survival of memory T cells, including auto-reactive clones, in inflammatory disorders. The aim of the study was to investigate the mechanisms of maintaining CD4+ memory T cells under normal and inflammatory conditions. We developed an in vitro model of inflammation, based on induction of pro-inflammatory cytokines, and then evaluated the effects of IL-7 upon purified sorted populations of CD4+Tcm and Tem under normal conditions and in vitro inflammatory model. IL-7 treatment promoted maintenance of CD4+Tcm phenotype in all variants of cultures. In the absence of contact with adherent cell fraction, the IL-7-induced proliferation of Tcm and Tem was slightly reduced, both under normal and inflammatory conditions, thus suggesting low sensitivity of memory T cells to contacts with MHC, and, probably, a requirement for additional signals to provide complete stimulation with IL-7. The last suggestion is also supported by data about CD127 and CD132 expression, i.e., in the absence of contact with MHC, the proportion of CD127+CD132+ cells was decreased in both subpopulations of CD4+ memory cells. Upon in vitro cultures, IL-7 contributed to decreased expression of CD127, and increased expression of CD132 on CD4+Tcm and Tem. We have evaluated the CD4+Tcm and Tem populations by affinity of T cell receptor (TCR), using the level of CD5 expression. Т cells with high TCR affinity for self-antigens are known to have higher expression of CD5. In comparison to Tem, the Tcm contained more CD5high cells. In cultures, IL-7 promoted a high level of CD5 expression on Tcm, which was comparable to levels observed in peripheral blood cells. High CD5 expression on Tem was observed after stimulation with IL-7 in the in vitro inflammatory model. In the absence of contact with MHC, the number of CD5high cells decreased among CD4+Tem and Tcm. Thus, CD4+Tcm cells with high affinity for autologous antigens are probably dependent on the presence of homeostatic factors, in particular, IL-7, and contacts with antigen-presenting cells (APCs). Under conditions of inflammation, no changes were revealed in the mechanism of maintaining CD4+Tcm, in contrast to CD4+Tem. Being less dependent on IL-7 under normal conditions, CD4+CD5highTem are accumulated in the presence of IL-7 under in vitro inflammatory conditions.
format	article
author	E. A. Blinova A. V. Kolerova V. E. Balyasnikov V. A. Kozlov
author_facet	E. A. Blinova A. V. Kolerova V. E. Balyasnikov V. A. Kozlov
author_sort	E. A. Blinova
title	In vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions
title_short	In vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions
title_full	In vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions
title_fullStr	In vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions
title_full_unstemmed	In vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions
title_sort	in vitro maintaining of cd4+ central and effector memory cells in normal and inflammatory conditions
publisher	SPb RAACI
publishDate	2020
url	https://doaj.org/article/e294256b11304047b945494ee99db0db
work_keys_str_mv	AT eablinova invitromaintainingofcd4centralandeffectormemorycellsinnormalandinflammatoryconditions AT avkolerova invitromaintainingofcd4centralandeffectormemorycellsinnormalandinflammatoryconditions AT vebalyasnikov invitromaintainingofcd4centralandeffectormemorycellsinnormalandinflammatoryconditions AT vakozlov invitromaintainingofcd4centralandeffectormemorycellsinnormalandinflammatoryconditions
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In vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions

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