Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia
The interplay between T- and B-cell compartments during naïve, effector and memory T cell maturation is critical for a balanced immune response. Primary B-cell immunodeficiency arising from X-linked agammaglobulinemia (XLA) offers a model to explore B cell impact on T cell subsets, starting from the...
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Format: | Article |
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Frontiers Media S.A.
2021-08-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.697307/full |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pavel V. Shelyakin Ksenia R. Lupyr Ksenia R. Lupyr Evgeny S. Egorov Ilya A. Kofiadi Dmitriy B. Staroverov Dmitriy B. Staroverov Sofya A. Kasatskaya Sofya A. Kasatskaya Sofya A. Kasatskaya Valeriia V. Kriukova Valeriia V. Kriukova Irina A. Shagina Irina A. Shagina Ekaterina M. Merzlyak Ekaterina M. Merzlyak Tatiana O. Nakonechnaya Elena A. Latysheva Irina A. Manto Musa R. Khaitov Sergey A. Lukyanov Dmitriy M. Chudakov Dmitriy M. Chudakov Dmitriy M. Chudakov Olga V. Britanova |
spellingShingle |
Pavel V. Shelyakin Ksenia R. Lupyr Ksenia R. Lupyr Evgeny S. Egorov Ilya A. Kofiadi Dmitriy B. Staroverov Dmitriy B. Staroverov Sofya A. Kasatskaya Sofya A. Kasatskaya Sofya A. Kasatskaya Valeriia V. Kriukova Valeriia V. Kriukova Irina A. Shagina Irina A. Shagina Ekaterina M. Merzlyak Ekaterina M. Merzlyak Tatiana O. Nakonechnaya Elena A. Latysheva Irina A. Manto Musa R. Khaitov Sergey A. Lukyanov Dmitriy M. Chudakov Dmitriy M. Chudakov Dmitriy M. Chudakov Olga V. Britanova Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia Frontiers in Immunology X-linked agammaglobulinemia (XLA) TCR repertoire T cell gene expression naïve regulatory T cells CDR3β features |
author_facet |
Pavel V. Shelyakin Ksenia R. Lupyr Ksenia R. Lupyr Evgeny S. Egorov Ilya A. Kofiadi Dmitriy B. Staroverov Dmitriy B. Staroverov Sofya A. Kasatskaya Sofya A. Kasatskaya Sofya A. Kasatskaya Valeriia V. Kriukova Valeriia V. Kriukova Irina A. Shagina Irina A. Shagina Ekaterina M. Merzlyak Ekaterina M. Merzlyak Tatiana O. Nakonechnaya Elena A. Latysheva Irina A. Manto Musa R. Khaitov Sergey A. Lukyanov Dmitriy M. Chudakov Dmitriy M. Chudakov Dmitriy M. Chudakov Olga V. Britanova |
author_sort |
Pavel V. Shelyakin |
title |
Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia |
title_short |
Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia |
title_full |
Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia |
title_fullStr |
Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia |
title_full_unstemmed |
Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia |
title_sort |
naïve regulatory t cell subset is altered in x-linked agammaglobulinemia |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-08-01 |
description |
The interplay between T- and B-cell compartments during naïve, effector and memory T cell maturation is critical for a balanced immune response. Primary B-cell immunodeficiency arising from X-linked agammaglobulinemia (XLA) offers a model to explore B cell impact on T cell subsets, starting from the thymic selection. Here we investigated characteristics of naïve and effector T cell subsets in XLA patients, revealing prominent alterations in the corresponding T-cell receptor (TCR) repertoires. We observed immunosenescence in terms of decreased diversity of naïve CD4+ and CD8+ TCR repertoires in XLA donors. The most substantial alterations were found within naïve CD4+ subsets, and we have investigated these in greater detail. In particular, increased clonality and convergence, along with shorter CDR3 regions, suggested narrower focused antigen-specific maturation of thymus-derived naïve Treg (CD4+CD45RA+CD27+CD25+) in the absence of B cells - normally presenting diverse self and commensal antigens. The naïve Treg proportion among naïve CD4 T cells was decreased in XLA patients, supporting the concept of impaired thymic naïve Treg selection. Furthermore, the naïve Treg subset showed prominent differences at the transcriptome level, including increased expression of genes specific for antigen-presenting and myeloid cells. Altogether, our findings suggest active B cell involvement in CD4 T cell subsets maturation, including B cell-dependent expansion of the naïve Treg TCR repertoire that enables better control of self-reactive T cells. |
topic |
X-linked agammaglobulinemia (XLA) TCR repertoire T cell gene expression naïve regulatory T cells CDR3β features |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.697307/full |
work_keys_str_mv |
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doaj-9b8c5dfdc92d41599dda081cf8de303f2021-08-19T12:02:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.697307697307Naïve Regulatory T Cell Subset Is Altered in X-Linked AgammaglobulinemiaPavel V. Shelyakin0Ksenia R. Lupyr1Ksenia R. Lupyr2Evgeny S. Egorov3Ilya A. Kofiadi4Dmitriy B. Staroverov5Dmitriy B. Staroverov6Sofya A. Kasatskaya7Sofya A. Kasatskaya8Sofya A. Kasatskaya9Valeriia V. Kriukova10Valeriia V. Kriukova11Irina A. Shagina12Irina A. Shagina13Ekaterina M. Merzlyak14Ekaterina M. Merzlyak15Tatiana O. Nakonechnaya16Elena A. Latysheva17Irina A. Manto18Musa R. Khaitov19Sergey A. Lukyanov20Dmitriy M. Chudakov21Dmitriy M. Chudakov22Dmitriy M. Chudakov23Olga V. Britanova24Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaCenter of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaFSBI “NRC Institute of Immunology” FMBA of Russia, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaInstitute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaCenter of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, RussiaInstitute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaCenter of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaInstitute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaInstitute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, RussiaInstitute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, RussiaFSBI “NRC Institute of Immunology” FMBA of Russia, Moscow, RussiaFSBI “NRC Institute of Immunology” FMBA of Russia, Moscow, RussiaFSBI “NRC Institute of Immunology” FMBA of Russia, Moscow, RussiaInstitute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaCenter of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, RussiaInstitute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaThe interplay between T- and B-cell compartments during naïve, effector and memory T cell maturation is critical for a balanced immune response. Primary B-cell immunodeficiency arising from X-linked agammaglobulinemia (XLA) offers a model to explore B cell impact on T cell subsets, starting from the thymic selection. Here we investigated characteristics of naïve and effector T cell subsets in XLA patients, revealing prominent alterations in the corresponding T-cell receptor (TCR) repertoires. We observed immunosenescence in terms of decreased diversity of naïve CD4+ and CD8+ TCR repertoires in XLA donors. The most substantial alterations were found within naïve CD4+ subsets, and we have investigated these in greater detail. In particular, increased clonality and convergence, along with shorter CDR3 regions, suggested narrower focused antigen-specific maturation of thymus-derived naïve Treg (CD4+CD45RA+CD27+CD25+) in the absence of B cells - normally presenting diverse self and commensal antigens. The naïve Treg proportion among naïve CD4 T cells was decreased in XLA patients, supporting the concept of impaired thymic naïve Treg selection. Furthermore, the naïve Treg subset showed prominent differences at the transcriptome level, including increased expression of genes specific for antigen-presenting and myeloid cells. Altogether, our findings suggest active B cell involvement in CD4 T cell subsets maturation, including B cell-dependent expansion of the naïve Treg TCR repertoire that enables better control of self-reactive T cells.https://www.frontiersin.org/articles/10.3389/fimmu.2021.697307/fullX-linked agammaglobulinemia (XLA)TCR repertoireT cell gene expressionnaïve regulatory T cellsCDR3β features |