Humanized Mice Reveal New Insights Into the Thymic Selection of Human Autoreactive CD8⁺ T Cells.

ABSTRACT: Thymic selection constitutes the first checkpoint in T-cell development to purge autoreactive T cells. Most of our understanding of this process comes from animal models because of the challenges of studying thymopoiesis and how T cell receptor (TCR) specificity impacts thymocyte phenotype in humans. We developed a humanized mouse model involving the introduction of autoreactive TCRs and cognate autoantigens that enables the analysis of selection of human T cells in human thymic tissue in vivo. Here, we describe the thymic development of MART1-specific autoreactive CD8⁺ T cells that normally escape deletion and how their phenotype and survival are affected by introduction of the missing epitope in the hematopoietic lineage. Expression of the epitope in a fraction of hemat

SUBMITTER: Li Y 

PROVIDER: S-EPMC6369192 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature