Unregulated antigen-presenting cell activation by T cells breaks self tolerance

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Title
Unregulated antigen-presenting cell activation by T cells breaks self tolerance
Author(s)
Jaeu Yi; Jisun Jung; Sung-Wook Hong; Jun Young Lee; Daehee Han; Kwang Soon Kim; Sprent J.; Charles D. Surh
Publication Date
2019-01
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.116, no.3, pp.1007 - 1016
Publisher
NATL ACAD SCIENCES
Abstract
T cells proliferate vigorously following acute depletion of CD4+ Foxp3+ T regulatory cells [natural Tregs (nTregs)] and also when naive T cells are transferred to syngeneic, nTreg-deficient Rag1−/− hosts. Here, using mice raised in an antigen-free (AF) environment, we show that proliferation in these two situations is directed to self ligands rather than food or commensal antigens. In both situations, the absence of nTregs elevates B7 expression on host dendritic cells (DCs) and enables a small subset of naive CD4 T cells with high self affinity to respond overtly to host DCs: bidirectional T/DC interaction ensues, leading to progressive DC activation and reciprocal strong proliferation of T cells accompanied by peripheral Treg (pTreg) formation. Likewise, high-affinity CD4 T cells proliferate vigorously and form pTregs when cultured with autologous DCs in vitro in the absence of nTregs: this anti-self response is MHCII/peptide dependent and elicited by the raised level of B7 on cultured DCs. The data support a model in which self tolerance is imposed via modulation of CD28 signaling and explains the pathological effects of superagonistic CD28 antibodies. © 2019 National Academy of Sciences. All Rights Reserved
URI
https://pr.ibs.re.kr/handle/8788114/6031
ISSN
0027-8424
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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