标题：Specificity requirements for selection and effector functions of CD25+4+ regulatory T cells in anti-myelin basic protein T cell receptor transgenic mice
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：12
页码：8213-8218
DOI：10.1073/pnas.122224799
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：CD25+4+ regulatory T cells (Treg) play an indispensable role in preventing autoimmunity. Little is known, however, about the antigen specificities required for their development and effector functions. Mice transgenic for an anti-myelin basic protein (MBP) T cell antigen receptor (TCR) spontaneously develop experimental autoimmune encephalomyelitis (EAE) when deficient for the RAG-1 gene (T/R-), whereas RAG-1-competent transgenic animals (T/R+) remain healthy, protected by CD4+ Treg-expressing endogenous TCRs. We have now investigated the role and specificity of CD25+4+ Treg in this system. The results show that T/R+ animals contain MBP-specific suppressive CD25+4+ cells, whereas T/R- do not. Adoptive transfer of CD25+4+ cells from nontransgenic or T/R+ donors into T/R- mice prevented the development of EAE. Surprisingly, transfer of nontransgenic CD25+4+ cells purified from T/R+ donors conferred only a limited protection, possibly because of their restricted repertoire diversity that we demonstrate here. Absence of transgenic CD25+4+ cells in animals deficient for endogenous TCR chains and analyses of endogenous TCR gene expression in subsets of CD4+ cells from T/R+ mice demonstrate that development of transgenic MBP-specific CD25+4+ Treg depends on the coexpression of endogenous TCR chains. Taken together, these results indicate that specificity to MBP is required for effector functions but is not sufficient for thymic selection/commitment of CD25+4+ Treg preventing EAE.
