Unusual selection and peripheral homeostasis for immunoregulatory CD 4 − CD 8 − T cells

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.