Negligible Role for Deletion Mediated by cDC1 in CD8 + T Cell Tolerance.

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.
(Copyright © 2019 by The American Association of Immunologists, Inc.)