Age and Latent Cytomegalovirus Infection Do Not Affect the Magnitude of De Novo SARS-CoV-2-Specific CD8+ T Cell Responses

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Jet van den Dijssel, Veronique A. L. Konijn, Mariël C Duurland, Rivka de Jongh, Lianne Koets, Barbera Veldhuisen, Hilde Raaphorst, Annelies W. Turksma, Julian J. Freen-van Heeren, Maurice Steenhuis, Theo Rispens, C Ellen van der Schoot, S. Marieke van Ham, Rene A. W. van Lier, Klaas P. J. M. van Gisbergen, Anja ten Brinke, Carolien E. van de Sandt
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Abstract

Immunosenescence, age-related immune dysregulation, reduces immunity upon vaccinations and infections. Cytomegalovirus (CMV) infection results in declining naïve (Tnaïve) and increasing terminally differentiated (Temra) T cell populations, further aggravating immune aging. Both immunosenescence and CMV have been speculated to hamper the formation of protective T-cell immunity against novel or emerging pathogens. The SARS-CoV-2 pandemic presented a unique opportunity to examine the impact of age and/or CMV on the generation of de novo SARS-CoV-2-specific CD8+ T cell responses in 40 younger (22–40 years) and 37 older (50–66 years) convalescent individuals. Heterotetramer combinatorial coding combined with phenotypic markers were used to study 35 SARS-CoV-2 epitope-specific CD8+ T cell populations directly ex vivo. Neither age nor CMV affected SARS-CoV-2-specific CD8+ T cell frequencies, despite reduced total CD8+ Tnaïve cells in older CMV- and CMV+ individuals. Robust SARS-CoV-2-specific central memory CD8+ T (Tcm) responses were detected in younger and older adults regardless of CMV status. Our data demonstrate that immune aging and CMV status did not impact the SARS-CoV-2-specific CD8+ T cell response. However, SARS-CoV-2-specific CD8+ T cells of older CMV- individuals displayed the lowest stem cell memory (Tscm), highest Temra and PD1+ populations, suggesting that age, not CMV, may impact long-term SARS-CoV-2 immunity.

Abstract Image

年龄和潜伏巨细胞病毒感染不影响新生sars - cov -2特异性CD8+ T细胞反应的大小
免疫衰老,与年龄相关的免疫失调,降低免疫接种和感染。巨细胞病毒(CMV)感染导致naïve (Tnaïve)下降和终末分化(Temra) T细胞群增加,进一步加剧免疫老化。据推测,免疫衰老和巨细胞病毒都阻碍了保护性t细胞免疫的形成,以对抗新的或新出现的病原体。SARS-CoV-2大流行提供了一个独特的机会来研究年龄和/或CMV对40名年轻(22-40岁)和37名年长(50-66岁)恢复期个体中新生SARS-CoV-2特异性CD8+ T细胞反应的影响。采用异源四聚体组合编码结合表型标记直接在体外研究35个SARS-CoV-2表位特异性CD8+ T细胞群。年龄和CMV均不影响sars - cov -2特异性CD8+ T细胞频率,尽管老年CMV-和CMV+个体的CD8+ Tnaïve细胞总数减少。无论CMV状态如何,在年轻人和老年人中都检测到强大的sars - cov -2特异性中枢记忆CD8+ T (Tcm)反应。我们的数据表明,免疫老化和CMV状态不影响sars - cov -2特异性CD8+ T细胞应答。然而,老年CMV个体的SARS-CoV-2特异性CD8+ T细胞显示出最低的干细胞记忆(Tscm),最高的Temra和PD1+群体,这表明年龄,而不是CMV,可能影响长期的SARS-CoV-2免疫。
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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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