TY - JOUR
T1 - Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla
AU - McCaughtry, T. M.
AU - Baldwin, T. A.
AU - Wilken, M. S.
AU - Hogquist, K. A.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2008/10/27
Y1 - 2008/10/27
N2 - The thymic medulla is generally held to be a specialized environment for negative selection. However, many self-reactive thymocytes first encounter ubiquitous self-antigens in the cortex. Cortical epithelial cells are vital for positive selection, but whether such cells can also promote negative selection is controversial. We used the HY cd4 model, where T cell receptor for antigen (TCR) expression is appropriately timed and a ubiquitous self-antigen drives clonal deletion in male mice. We demonstrated unambiguously that this deletion event occurs in the thymic cortex. However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation. We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation. Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c + cortical dendritic cells, and elimination of such cells impaired deletion.
AB - The thymic medulla is generally held to be a specialized environment for negative selection. However, many self-reactive thymocytes first encounter ubiquitous self-antigens in the cortex. Cortical epithelial cells are vital for positive selection, but whether such cells can also promote negative selection is controversial. We used the HY cd4 model, where T cell receptor for antigen (TCR) expression is appropriately timed and a ubiquitous self-antigen drives clonal deletion in male mice. We demonstrated unambiguously that this deletion event occurs in the thymic cortex. However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation. We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation. Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c + cortical dendritic cells, and elimination of such cells impaired deletion.
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U2 - 10.1084/jem.20080866
DO - 10.1084/jem.20080866
M3 - Article
C2 - 18936237
AN - SCOPUS:58149154739
VL - 205
SP - 2575
EP - 2584
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 11
ER -