mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-EOC-16849mimmun-3089Research ArticleКРАТКИЕ СООБЩЕНИЯSHORT COMMUNICATIONSЭкспрессия чек-поинт-молекул популяциями регуляторных Т-клеток при множественной миеломеExpression of checkpoint molecules by regulatory T cells in multiple myelomaОстанинА. А.OstaninA. A.

Останин Александр Анатольевич – д.м.н., профессор, главный научный сотрудник.

630099, Новосибирск, ул. Ядринцевская, 14

Тел.: 8 (383) 228-21-01

Aleksander A. Ostanin - PhD, MD (Medicine), Professor, Chief Research Associate, Research Institute of Fundamental and Clinical Immunology.

14 Yadrintsevskaya St Novosibirsk 630099

Phone +7 (383) 228-21-01

ostanin62@mail.ruБатороваД. С.BatorovaD. S.

К.м.н., врач-гематолог.

Новосибирск

PhD (Medicine), Hematologist, Research Institute of Fundamental and Clinical Immunology.

Novosibirsk

СизиковаС. А.SizikovaS. A.

К.м.н., врач-гематолог.

Новосибирск

PhD (Medicine), Hematologist, Research Institute of Fundamental and Clinical Immunology.

Novosibirsk

КруковичА. Б.KrukovichA. B.

Клинический ординатор.

Новосибирск

Medical Resident, Research Institute of Fundamental and Clinical Immunology.

Novosibirsk

ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии»РоссияResearch Institute of Fundamental and Clinical ImmunologyRussian Federation202421092024265913918Copyright © Останин А.А., Баторова Д.С., Сизикова С.А., Крукович А.Б., 20242024Останин А.А., Баторова Д.С., Сизикова С.А., Крукович А.Б.Ostanin A.A., Batorova D.S., Sizikova S.A., Krukovich A.B.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/3089

При множественной миеломе (ММ) повышено содержание Т-лимфоцитов, экспрессирующих «чек-поинт»-молекулы PD-1, TIM-3, LAG-3 и др. Важную роль в патогенезе ММ также играют регуляторные Т-клетки (Treg), способные подавлять противоопухолевый иммунный ответ. Подобно эффекторным Т-лимфоцитам, часть Treg экспрессирует чек-поинт-рецепторы PD-1, TIM-3 и др., однако биологический смысл такой экспрессии, а также последствия блокады этих рецепторов не ясны. Также остается не изученным значение регуляторных Т-клеток I типа (Tr1), продуцирующих иммуносупрессорный цитокин интерлейкин-10, при ММ. Целью настоящей работы было изучение содержания PD-1- и TIM-3-экспрессирующих Treg и Tr1 у больных ММ.

В исследование были включены 36 больных ММ и 24 сопоставимых здоровых донора. Содержание популяций CD4+CD25hiCD127-FoxP3+Treg и IL-10-подуцирующих CD4+IL-10+Tr1, экспрессирующих PD-1 и TIM-3, оценивали в периферической крови (ПК) и костном мозге (КМ) методом проточной цитометрии.

Относительное содержание циркулирующих CD4+CD25hiCD127-FoxP3+Treg и IL-10-подуцирующих CD4+IL-10+Tr1 было значимо выше у больных ММ по сравнению со здоровыми донорами. Было отмечено более высокое по сравнению с Treg относительное содержание IL-10-продуцирующих Т-лимфоцитов. Относительное содержание Treg и Tr1 в образцах КМ значимо не отличалось от показателей ПК. Доля Treg, экспрессирующих PD-1 и TIM-3, у больных ММ значимо не отличалась от значений здоровых доноров. Содержание PD-1- и TIM-3-позитивных CD4+IL-10+Т-клеток было значимо выше в образцах ПК больных ММ по сравнению с донорами.

IL-10-продуцирующие CD4+Т-клетки составляют значительную долю Т-лимфоцитов в ПК и КМ больных ММ и могут играть важную роль в патогенезе ММ. Их содержание превосходит количество CD4+CD25hiCD127-FoxP3+Treg. Относительно небольшое количество Treg экспрессирует чек-поинт-рецепторы PD-1 и TIM-3, не отличаясь от показателей доноров. Доля PD-1-/TIM-3-позитивных клеток составляет ~20 % CD4+IL-10+Т-клеток и значимо превышает значения здоровых лиц.

In multiple myeloma (MM), the content of T lymphocytes expressing “checkpoint” molecules PD-1, TIM-3, LAG-3, etc. is increased. Regulatory T cells (Treg) can suppress antitumor immune response and play a sufficient role in MM pathogenesis. Like effector T lymphocytes, some Tregs express checkpoint receptors PD-1, TIM-3, etc., however, the biological meaning of such expression, as well as the consequences of blockade of these receptors, are not clear. The significance of type I regulatory T cells (Tr1), which produce the immunosuppressive cytokine interleukin-10, in MM also remains unexplored. The purpose of this work was to study the content of PD-1- and TIM-3-expressing Tregs and Tr1 in patients with MM. The study included 36 patients with MM and 24 matched healthy donors. The content of CD4+CD25hiCD127-FoxP3+Tregs and IL-10-producing CD4+IL-10+Tr1 populations expressing PD-1 and TIM-3 was assessed in peripheral blood (PB) and bone marrow (BM) by flow cytometry. The relative content of circulating CD4+CD25hiCD127-FoxP3+Tregs and IL-10-producing CD4+IL-10+Tr1 was significantly higher in MM patients compared to healthy donors. A higher relative content of IL-10-producing T lymphocytes was noted compared to Treg. The relative content of Tregs and Tr1 in BM samples did not differ significantly from PB values. The proportion of Tregs expressing PD-1 and TIM-3 in patients with MM did not differ significantly from the values in healthy donors. The content of PD-1- and TIM-3-positive CD4+IL-10+T cells was significantly higher in PB samples from MM patients compared to donors.

IL-10-producing CD4+T cells constitute a significant proportion of T lymphocytes in the PB and BM of patients with MM and may play an important role in the pathogenesis of MM. Their content exceeds that of CD4+CD25hiCD127-FoxP3+Treg. A relatively small number of Tregs express the checkpoint receptors PD-1 and TIM-3, no different from donors. The proportion of PD-1-/TIM-3-positive cells is ~20% of CD4+IL-10+T cells and significantly exceeds the values of healthy individuals.

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