{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:50:31Z","timestamp":1793303431056,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The interplay between T- and B-cell compartments during na\u00efve, 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 na\u00efve 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 na\u00efve CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>TCR repertoires in XLA donors. The most substantial alterations were found within na\u00efve CD4<jats:sup>+<\/jats:sup>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 na\u00efve T<jats:sub>reg<\/jats:sub>(CD4<jats:sup>+<\/jats:sup>CD45RA<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>) in the absence of B cells - normally presenting diverse self and commensal antigens. The na\u00efve T<jats:sub>reg<\/jats:sub>proportion among na\u00efve CD4 T cells was decreased in XLA patients, supporting the concept of impaired thymic na\u00efve T<jats:sub>reg<\/jats:sub>selection. Furthermore, the na\u00efve T<jats:sub>reg<\/jats:sub>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 na\u00efve Treg TCR repertoire that enables better control of self-reactive T cells.<\/jats:p>","DOI":"10.3389\/fimmu.2021.697307","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T12:09:42Z","timestamp":1629374982000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Na\u00efve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia"],"prefix":"10.3389","volume":"12","author":[{"given":"Pavel V.","family":"Shelyakin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ksenia R.","family":"Lupyr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny 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