mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2018-5-613-620mimmun-1630Research ArticleОБЗОРЫREVIEWSИММУНОЛОГИЧЕСКАЯ ПАМЯТЬ: РОЛЬ РЕГУЛЯТОРНЫХ КЛЕТОК TREGIMMUNOLOGICAL MEMORY: THE ROLE OF REGULATORY CELLS (TREGS)ОлейникE. К.OleinikE. K.

д.б.н., доцент, главный научный сотрудник, руководитель группы иммунологии.

185910, Россия, Республика Карелия, г. Петрозаводск, ул. Пушкинская, 11.

PhD, MD (Biology), Associate Professor, Senior Research Associate, Head, Immunology Group.

185910, Russian Federation, Republic of Karelia, Petrozavodsk, Pushkinskaya str., 11.

ole@krc.karelia.ruЧуровА. В.ChurovA. V.

к.б.н., научный сотрудник группы иммунологии.

PhD (Biology), Research Associate, Immunology Group.

ОлейникВ. М.OleinikV. M.

д.б.н., ведущий научный сотрудник группы иммунологии.

PhD, MD (Biology), Leading Research Associate, Immunology Group.

Институт биологии Карельского научного центра Российской академии наук.РоссияInstitute of Biology, Karelian Research Centre, Russian Academy of Sciences.Russian Federation201804112018205613620Copyright © Олейник E.К., Чуров А.В., Олейник В.М., 20182018Олейник E.К., Чуров А.В., Олейник В.М.Oleinik E.K., Churov A.V., Oleinik V.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1630

Т-клетки памяти необходимы для развития иммунного ответа и представляют собой одну из наиболее многочисленных популяций Т-лимфоцитов человека. Регуляторные Т-клетки (Treg), напротив, выполняют функцию завершения адаптивного иммунного ответа и обеспечения толерантности к собственным антигенам. Эти группы клеток представлены разными субпопуляциями и присутствуют в организме в течение всей жизни. Однако сегодня еще нет ясного понимания того, как формируются взаимосвязи между этими группами клеток. В работе рассматриваются возможные пути развития и поддержания CD4+ Т-клеточной памяти с участием Treg-клеток. Обсуждаются разные механизмы дифференцировки Т-клеток памяти, Treg-клеток и недавно открытых Treg-клеток памяти, сравниваются их функциональные и молекулярно-генетические характеристики. Разделение клеток по функциональному профилю позволяет отметить параллели между T-клетками памяти и Treg-клетками: и те и другие представлены центральными циркулирующими популяциями (Tc), эффекторными, которые мигрируют в ткани (Te), и тканево-резидентными (Tr), пребывающими в тканях на периферии. Сходная структурная организация Tregs и Т-клеток памяти, существование переходных форм тканево-резидентных субпопуляций Tregs со свойствами клеток памяти может свидетельствовать о тесной взаимосвязи между данными группами лимфоцитов. Одним из вариантов такой связи может быть существование конверсии CD4+T-клеток памяти с образованием Treg-клеток, экспрессирующих транскрипционный фактор FoxP3. Treg-клетки памяти, обладающие свойствами и Т-клеток памяти, и Treg-клеток, могут представлять собой переходный этап дифференцировки. С другой стороны, Treg-клетки могут дифференцироваться независимо от Т-клеток памяти и накапливаться в течение жизни в виде Treg-клеток памяти, так как их супрессорная функция является столь же постоянно необходимой, как и готовность Т-клеток памяти развивать иммунный ответ. Возможно, часть Treg-клеток уже в тимусе проходит отбор и конститутивно экспрессирует антигенраспознающие рецепторы TCR, имеющие сродство с периферическими тканями. В дальнейшем эти коммитированные клетки могут расселяться в соответствующих тканях и становятся тканево-резидентными Treg-клетками, которые поддерживают региональную Т-клеточную память. Система Tregклеток может представлять собой зеркальное отражение структурной организации Т-клеток памяти, но с обратным знаком – знаком супрессии. Количественное соотношение Тreg-клеток и Т-клеток памяти (CD4+CD45RO+CD25hiFoxP3+/CD4+CD45RO+CD25-FoxP3-), возможно, является важным критерием для оценки функционального состояния иммунной системы. Поддержание баланса между этими функционально противоположными типами клеток должно обеспечивать устойчивое функционирование иммунной системы.

Memory T cells are necessary for development of the immune response and represent one of the most numerous population of human T lymphocytes. On the contrary, suppressive regulatory T cells (Tregs) may terminate the immune response and help to maintain tolerance to self-antigens. These important groups of cells are consisting of different subpopulations and retaining throughout life. However, today there is yet no clear understanding of how the relations between these two groups of cells are formed. In this work we consider possible ways of development and maintenance of CD4+ T cell memory and role of Tregs in these processes. Mechanisms of a differentiation of memory T cells, Tregs and recently described memory Tregs are discussed. The functional and genetic characteristics of these cells are compared. Division of cells according to the functional profile allows drawing parallels between memory T cells and Tregs. These two groups are consisted of central circulating populations (Tc), effector which can migrate toward specific tissues (Te) and tissue-resident cells (Tr), which are staying in peripheral tissues. The similar structural organization of Tregs and memory T cells, existence of transitional forms of tissue-resident Treg subpopulations with properties of memory cells assumes existence of close interrelation between these groups of lymphocytes. The conversion of CD4+ memory T cells into FoxP3-expressing Tregs is one of possible mechanisms of communication between these two groups. The memory Treg-cells with T cell and memory Treg-cell properties can represent a transitional stage of differentiation. On the other side, Treg cells can differentiate independently of memory T cells and accumulate during life in the form of memory Treg cells. The supressor function of Tregs is also necessary as well as function of memory T cells to develop the immune response. It is possible, that a subset of Treg cells undergoes selection in thymus and constitutively express TCR-receptors having affinity with peripheral tissues. Further, these committed cells can be settled into tissues and become tissue-resident Treg cells which maintain regional T cell memory. Tregs can represent the “mirror image” of the structural organization of memory T cells, but with the return sign – the sign of suppression. The quantitative ratio of Tregs and memory T cells (CD4+CD45RO+CD25hiFoxP3+/CD4+CD45RO+CD25-FoxP3-), perhaps, is important criterion for functional assessment of immune system. The balance between these functionally opposite cell subsets has to provide stable functioning of immune system.

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The authors declare that there are no conflicts of interest present.