The endogenous repertoire harbors self-reactive CD4(+) T cell clones that adopt a follicular helper T cell-like phenotype at steady state Journal Article
| Authors: | Lee, V.; Rodriguez, D. M.; Ganci, N. K.; Zeng, S.; Ai, J.; Chao, J. L.; Walker, M. T.; Miller, C. H.; Klawon, D. E. J.; Schoenbach, M. H.; Kennedy, D. E.; Maienschein-Cline, M.; Socci, N. D.; Clark, M. R.; Savage, P. A. |
| Article Title: | The endogenous repertoire harbors self-reactive CD4(+) T cell clones that adopt a follicular helper T cell-like phenotype at steady state |
| Abstract: | The T cell repertoire of healthy mice and humans harbors self-reactive CD4+ conventional T (Tconv) cells capable of inducing autoimmunity. Using T cell receptor profiling paired with in vivo clonal analysis of T cell differentiation, we identified Tconv cell clones that are recurrently enriched in non-lymphoid organs following ablation of Foxp3+ regulatory T (Treg) cells. A subset of these clones was highly proliferative in the lymphoid organs at steady state and exhibited overt reactivity to self-ligands displayed by dendritic cells, yet were not purged by clonal deletion. These clones spontaneously adopted numerous hallmarks of follicular helper T (TFH) cells, including expression of Bcl6 and PD-1, exhibited an elevated propensity to localize within B cell follicles at steady state, and produced interferon-γ in non-lymphoid organs following sustained Treg cell depletion. Our work identifies a naturally occurring population of self-reactive TFH-like cells and delineates a previously unappreciated fate for self-specific Tconv cells. © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | mouse; phenotype; animal; animals; mice; cell differentiation; regulatory t lymphocyte; t-lymphocytes, regulatory; autoimmunity; t-lymphocytes, helper-inducer; cell clone; clone cells; helper cell; humans; human; tfh cell; t follicular helper cells |
| Journal Title: | Nature Immunology |
| Volume: | 24 |
| Issue: | 3 |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-03-01 |
| Start Page: | 487 |
| End Page: | 500 |
| Language: | English |
| DOI: | 10.1038/s41590-023-01425-0 |
| PUBMED: | 36759711 |
| PROVIDER: | scopus |
| PMCID: | PMC9992328 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PDF -- Source: Scopus |
