Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia.

Autor: Shelyakin PV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia., Lupyr KR; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia., Egorov ES; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia., Kofiadi IA; FSBI 'NRC Institute of Immunology' FMBA of Russia, Moscow, Russia., Staroverov DB; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia., Kasatskaya SA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia.; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia., Kriukova VV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia., Shagina IA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia., Merzlyak EM; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia., Nakonechnaya TO; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia., Latysheva EA; FSBI 'NRC Institute of Immunology' FMBA of Russia, Moscow, Russia., Manto IA; FSBI 'NRC Institute of Immunology' FMBA of Russia, Moscow, Russia., Khaitov MR; FSBI 'NRC Institute of Immunology' FMBA of Russia, Moscow, Russia., Lukyanov SA; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia., Chudakov DM; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia.; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia., Britanova OV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2021 Aug 19; Vol. 12, pp. 697307. Date of Electronic Publication: 2021 Aug 19 (Print Publication: 2021).
DOI: 10.3389/fimmu.2021.697307
Abstrakt: 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 T reg (CD4 + CD45RA + CD27 + CD25 + ) in the absence of B cells - normally presenting diverse self and commensal antigens. The naïve T reg proportion among naïve CD4 T cells was decreased in XLA patients, supporting the concept of impaired thymic naïve T reg selection. Furthermore, the naïve T reg 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Shelyakin, Lupyr, Egorov, Kofiadi, Staroverov, Kasatskaya, Kriukova, Shagina, Merzlyak, Nakonechnaya, Latysheva, Manto, Khaitov, Lukyanov, Chudakov and Britanova.)
Databáze: MEDLINE
Externí odkaz: