First Author | MacNabb BW | Year | 2019 |
Journal | J Immunol | Volume | 202 |
Issue | 9 | Pages | 2628-2635 |
PubMed ID | 30902900 | Mgi Jnum | J:274887 |
Mgi Id | MGI:6296828 | Doi | 10.4049/jimmunol.1801621 |
Citation | MacNabb BW, et al. (2019) Negligible Role for Deletion Mediated by cDC1 in CD8(+) T Cell Tolerance. J Immunol 202(9):2628-2635 |
abstractText | Deletion of CD8(+) T cells by dendritic cells (DCs) is recognized as a critical mechanism of immune tolerance to self-antigens. Although DC-mediated peripheral deletion of autoreactive CD8(+) T cells has been demonstrated using T cells reactive to model Ags, its role in shaping the naturally occurring polyclonal CD8(+) T cell repertoire has not been defined. Using Batf3(-/-) mice lacking cross-presenting CD8alpha(+) and CD103(+) DCs (also known as type 1 conventional [cDC1]), we demonstrate that peripheral deletion of CD8(+) T cells reactive to a model tissue Ag is dependent on cDC1. However, endogenous CD8(+) T cells from the periphery of Batf3(-/-) mice do not exhibit heightened self-reactivity, and deep TCR sequencing of CD8(+) T cells from Batf3(-/-) and Batf3(+/+) mice reveals that cDC1 have a minimal impact on shaping the peripheral CD8(+) T cell repertoire. Thus, although evident in reductionist systems, deletion of polyclonal self-specific CD8(+) T cells by cDC1 plays a negligible role in enforcing tolerance to natural self-ligands. |