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 CD8α+ 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.
CITATION STYLE
MacNabb, B. W., Kline, D. E., Albright, A. R., Chen, X., Leventhal, D. S., Savage, P. A., & Kline, J. (2019). Negligible Role for Deletion Mediated by cDC1 in CD8+ T Cell Tolerance. The Journal of Immunology, 202(9), 2628–2635. https://doi.org/10.4049/jimmunol.1801621
Mendeley helps you to discover research relevant for your work.