Positive Selection of Extrathymically Developed T Cells by Self-antigens

Abstract

Most T cells develop through the thymus, where they undergo positive and negative selection. Some peripheral T cells are known to develop in the absence of thymus, but there is insufficient information about their selection. To analyze the selection of extrathymically developed T cells, we reconstituted thymectomized male or female recipient mice with bone marrow cells of mice transgenic for male H-Y antigen–specific T cell receptor (TCR). It was revealed that the T cells bearing self-antigen–specific TCR were not deleted in thymectomized male recipients. More importantly, the absence of H-Y antigen–specific T cells in thymectomized female recipients suggests positive selection of extrathymically developed T cells by the self-antigen. The extrathymically developed T cells in male mice expressed interleukin (IL)-2 receptor β chain (IL-2Rβ) and intermediate levels of CD3 (CD3int) but were natural killer cell (NK)1.1−. They rapidly produced interferon γ but not IL-4 after TCR cross-linking. Furthermore, a similar pattern of cytokine production was observed in CD3intIL-2Rβ+NK1.1− cells in normal mice which have been shown to develop extrathymically. These results suggest that extrathymically developed CD3intIL-2Rβ+NK1.1− cells in normal mice are also positively selected by self-antigens.

TCR-Independent Activation of Extrathymically Developed, Self Antigen-Specific T Cells by IL-2/IL-15

“…1 Fig. 1), neither of which developed in the absence of the thymus, as we have reported previously (7).…”

“…, and high levels of CD44 (CD44 high ) similar to the extrathymically developed T cells in normal mice (7). In this study, we first addressed whether all of the T3.70 ϩ CD8 ϩ cells in unmanipulated male H-Y transgenic mice have such phenotypes of surface molecule expression.…”

Identification of CD25+ γδ T Cells As Fetal Thymus-Derived Naturally Occurring IL-17 Producers

“…␥␦ T cells and invariant NKT cells are also similar in their functions as innate lymphocytes that play a role in early protection against infection. Innate lymphocytes also include NK cells as well as memory phenotype CD8 T cells, which rapidly secrete IFN-␥ and a part of latter are suggested to be self-specific (45). NKT cells as well as IL-17-producing ␥␦ T cells express memory markers (43).…”

Self-reactive memory-phenotype CD8 T cells exhibit both MHC-restricted and non-MHC-restricted cytotoxicity: a role for the T-cell receptor and natural killer cell receptors

“…7,8 von Boehmer et al 5 have shown that the development of CD8 lo cells is thymus dependent, since the cells are not found in male H-2 b H-Y nude mice. By contrast, Yamada et al 6 found that CD8 lo cells developed normally in thymectomized male but not female H-2 b mice. Another unusual feature of these CD8 lo T cells is that they proliferate in response to cytokines such as IL-2 and IL-15 in an antigen-independent manner.…”

“…4,5 The CD8 lo cells are selfreactive, as they expand after transfer into male but not female H-2 b nude mice. 5 These cells express high levels of CD44 5 and interleukin-2 receptor ␤ (IL-2R␤; CD122) 6 that are characteristic of memory T cells. However, they differ from conventional memory T cells in that they are more refractory to activation by antigen compared with naive T cells.…”