Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1796010.15789/2220-7619-CTC-17960ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИResearch ArticleCD8 T cells in mice with different genetic susceptibility to anti-tuberculous immune responseУчастие лимфоцитов CD8 в противотуберкулезном иммунном ответе у мышей с разным уровнем генетической восприимчивости к инфекцииLogunovaN. N.ЛогуноваН. Н.
Russian Federation

PhD (Medicine), Senior Researcher, Laboratory of Immunogenetics

к.м.н., старший научный сотрудник лаборатории иммуногенетики

nadezda2004@yahoo.comKapinaM. A.КапинаМ. А.
Russian Federation

PhD (Biology), Senior Researcher, Laboratory of Immunogenetics

к.б.н., старший научный сотрудник лаборатории иммуногенетики

makapina@mail.ruLingeI. A.ЛингеИ. А.
Russian Federation

PhD (Biology), Leading Researcher, Laboratory of Immunogenetics, Immunology Department

к.б.н., ведущий научный сотрудник лаборатории иммуногенетики отдела иммунологии

iralinge@gmail.comKondratievaE. V.КондратьеваЕ. В.
Russian Federation

PhD (Biology), Senior Researcher, Laboratory of Immunogenetics, Immunology Department

к.б.н., старший научный сотрудник лаборатории иммуногенетики отдела иммунологии

alyonakondratyeva74@gmail.comAptAlexander S.АптАлександр Соломонович
Russian Federation

DSc (Biology), Professor, Head of the Laboratory of Immunogenetics, Immunology Department

д.б.н., профессор, зав. лабораторией иммуногенетики отдела иммунологии

alexapt0151@gmail.comCentral Tuberculosis Research InstituteФГБНУ Центральный научно-исследовательский институт туберкулеза08082025081220251558718800907202502082025Copyright ©; 2025, Logunova N.N., Kapina M.A., Linge I.A., Kondratieva E.V., Apt A.S.Copyright ©; 2025, Логунова Н.Н., Капина М.А., Линге И.А., Кондратьева Е.В., Апт А.С.2025Logunova N.N., Kapina M.A., Linge I.A., Kondratieva E.V., Apt A.S.Логунова Н.Н., Капина М.А., Линге И.А., Кондратьева Е.В., Апт А.С.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/17960

In spite of decades of studying the role for CD8+ T-cells in response to tuberculosis (TB) infection, it remains only partly understood. Even less is known how the level of host genetic susceptibility to TB infection influences the involvement of these cells in immune response. Our lab established MHC II-congenic mouse strains with different levels of genetic susceptibility to TB infection dependent exclusively upon quantitative and qualitative differences in organization of relevant CD4 T-cell populations and lacking major defects in immune systems. In the present work, we investigated how the in vivo lack of CD8+ T-cells affects related capacity to combat TB infection. To this end, we developed a novel double-congenic mouse strain В6.I-9.3-β2M–/– that lacks CD8 T cells due to a knockout mutation in the gene encoding β2-microglobulin and differs from the parental B6 strain by the MHC II allele. We performed a comparative study of TB development and immune response using four mouse strains: the ancestor В6 and B6.I-9.3 pair vs. CD8-deficient В6-β2M–/– and В6.I-9.3-β2M–/– pair. CD8 T-cell deficiency did not alter lung mycobacterial multiplication during the first 4 weeks post TB challenge; however, at day 90 lung mycobacterial population increased to significantly higher levels in В6-β2M–/– compared to B6 mice. Post-infection life span of both CD8 T-cell-deficient mouse strains was dramatically shorter than that of the wild type animals. En mass, negative effects of CD8 cell deficiency looked more pronounced on the MHC II allele background, which in the presence of CD8 cells is associated with better protection against infection. In addition, the lack of CD8+ cells resulted in significantly decreased size of TNF-positive CD4+ T-cell populations in mice from both β2M–/– strains at week 4 post-challenge. This is consistent with a previously non-described helper function of CD8 cells for the TNF synthesis by CD4 cells. We discuss the results obtained within the context of dynamical interactions between T-cell populations during chronic TB infection.

Роль Т-лимфоцитов CD8+ в иммунном ответе на туберкулезную инфекцию (ТБ) остается не до конца понятной, несмотря на десятки лет работы над этой проблемой. Почти ничего не известно о влиянии на их участие в ответе на инфекцию уровня генетической восприимчивости хозяина к ТБ. В нашей лаборатории выведены конгенные по MHC II линии мышей с разным уровнем генетической чувствительности к ТБ, обусловленным исключительно количественными и качественными отличиями в составе популяции CD4 Т-клеток и не несущие грубых дефектов в иммунной системе. В данной работе мы исследовали, как влияет избирательное отсутствие клеток CD8+ на уровень протекции у этих животных. Для этого была получена новая двойная конгенная линия мышей В6.I-9.3-β2M–/–, которая не имеет Т-клеток CD8 из-за нокаут-мутации в гене, кодирующем β2-микроглобулин, и отличается от родительской линии В6 по аллелю гена Н2-А МНС класса II. Мы провели сравнительный анализ течения ТБ и иммунного ответа на инфекцию, используя четыре линии мышей — исходную пару В6 и B6.I-9.3 и лишенную Т-клеток CD8 пару В6-β2M–/– и В6.I-9.3-β2M–/–. Дефицит Т-клеток CD8 не влиял на размножение микобактерий в легких в течение первых четырех недель после заражения, но через 90 дней в легких мышей В6-β2M–/– популяция микобактерий вырастала достоверно сильнее, чем у мышей В6. Срок выживания мышей обеих линий с дефицитом клеток CD8 оказался гораздо короче, чем мышей дикого типа. В целом, негативное влияние отсутствия клеток CD8 сильнее проявлялось на фоне аллеля MHC II, обеспечивающего более эффективный защитный ответ на инфекцию. Кроме того, при отсутствии клеток CD8+ на четвертой неделе после заражения достоверно снижалась доля TNF-положительных клеток CD4 у мышей обеих линий, несущих мутацию β2M–/–, указывая на ранее не описанную вспомогательную роль клеток CD8 в синтезе TNF клетками CD4. Полученные данные обсуждаются в контексте динамических взаимодействий между популяциями Т-лимфоцитов при хронической туберкулезной инфекции.

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