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Unusual selection and peripheral homeostasis for immunoregulatory CD 4 − CD 8 − T cells
Author(s) -
Dugas Véronique,
ChabotRoy Geneviève,
Beauchamp Claudine,
GuimontDesrochers Fanny,
Hillhouse Erin E.,
Liston Adrian,
Lesage Sylvie
Publication year - 2013
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12064
Subject(s) - biology , t cell receptor , major histocompatibility complex , t cell , microbiology and biotechnology , negative selection , antigen , receptor , immunology , immune system , genetics , gene , genome
Summary Immunoregulatory CD 4 − CD 8 − (double‐negative; DN ) T cells exhibit a unique antigen‐specific mode of suppression, yet the ontogeny of DN T cells remains enigmatic. We have recently shown that 3 A 9 T ‐cell receptor ( TCR ) transgenic mice bear a high proportion of immunoregulatory 3 A 9 DN T cells, facilitating their study. The 3 A 9 TCR is positively selected on the H 2 k MHC haplotype, is negatively selected in mice bearing the cognate antigen, namely hen egg lysozyme, and there is absence of positive selection on the H 2 b MHC haplotype. Herein, we take advantage of this well‐defined 3 A 9 TCR transgenic model to assess the thymic differentiation of DN T cells and its impact on determining the proportion of these cells in secondary lymphoid organs. We find that the proportion of DN T cells in the thymus is not dictated by the nature of the MHC ‐selecting haplotype. By defining DN T ‐cell differentiation in 3 A 9 TCR transgenic CD 47‐deficient mice as well as in mice bearing the NOD . H 2 k genetic background, we further demonstrate that the proportion of 3 A 9 DN T cells in the spleen is independent of the MHC selecting haplotype. Together, our findings suggest that immunoregulatory DN T cells are subject to rules distinct from those imposed upon CD 4 T cells.