Dissociation of thymic positive and negative selection in transgenic mice expressing major histocompatibility complex class I molecules exclusively on thymic cortical epithelial cells

被引:46
作者
Capone, M
Romagnoli, P
Beermann, F
MacDonald, HR
van Meerwijk, JPM
机构
[1] CHU Purpan, INSERM, U395, F-31024 Toulouse 3, France
[2] Univ Lausanne, Ludwig Inst Canc Res, Lausanne Branch, CH-1066 Epalinges, Switzerland
[3] Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland
[4] Univ Toulouse 3, Fac Life Sci UFR SVT, F-31062 Toulouse, France
关键词
D O I
10.1182/blood.V97.5.1336
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thymic positive and negative selection of developing T lymphocytes confronts us with a paradox: How can a T-cell antigen receptor (TCR)-major histocompatibility complex (MHC)/peptide interaction in the former process lead to transduction of signals allowing for cell survival and in the latter induce programmed cell death or a hyporesponsive state known as anergy? One of the hypotheses put forward states that the outcome of a TCR-MHC/peptide interaction depends on the cell type presenting the selecting ligand to the developing thymocyte. Here we describe the development and lack of self-tolerance of CD8(+) T lymphocytes in transgenic mice expressing MHC class I molecules in the thymus exclusively on cortical epithelial cells. Despite the absence of MHC class I expression on professional antigen-presenting cells, normal numbers of CD8(+) cells were observed in the periphery. Upon specific activation, transgenic CD8(+) T cells efficiently lysed syngeneic MHC class I+ targets in vitro and in vivo, indicating that thymic cortical epithelium (in contrast to medullary epithelium and antigen-presenting cells of hematopoietic origin) is incapable of tolerance induction. Thus, compartmentalization of the antigen-presenting cells involved in thymic positive selection and tolerance induction can (at least in part) explain the positive/negative selection paradox. (Blood, 2001;97:1336-1342) (C) 2001 by The American Society of Hematology.
引用
收藏
页码:1336 / 1342
页数:7
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