title: Positive selection of self-antigen-specific CD8+ T cells by hematopoietic cells.
abstract: In contrast to thymic epithelial cells, which induce the positive selection of conventional CD8(+) T cells, hematopoietic cells (HCs) select innate CD8(+) T cells whose Ag specificity is not fully understood. Here we show that CD8(+) T cells expressing an H-Y Ag-specific Tg TCR were able to develop in mice in which only HCs expressed MHC class I, when HCs also expressed the H-Y Ag. These HC-selected self-specific CD8(+) T cells resemble innate CD8(+) T cells in WT mice in terms of the expression of memory markers and effector functions, but are phenotypically distinct from the thymus-independent CD8(+) T-cell population. The peripheral maintenance of H-Y-specific CD8(+) T cells required presentation of the self-Ag and IL-15 on HCs. HC-selected CD8(+) T cells in mice lacking the Tg TCR also showed these features. Furthermore, by using MHC class I tetramers with a male Ag peptide, we found that self-Ag-specific CD8(+) T cells in TCR non-Tg mice could develop via HC-induced positive selection, supporting results obtained from H-Y TCR Tg mice. These findings indicate the presence of self-specific CD8(+) T cells that are positively selected by HCs in the peripheral T-cell repertoire.
authors: Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. hisakata@bioreg.kyushu-u.ac.jp
authors: Hisakata
authors: H
authors: Yamada
authors: Kensuke
authors: K
authors: Shibata
authors: Koji
authors: K
authors: Sakuraba
authors: Kenjiro
authors: K
authors: Fujimura
authors: Yasunobu
authors: Y
authors: Yoshikai
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D006182:H-Y Antigen / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D019409:Interleukin-15 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011946:Receptors, Antigen / Q000096:biosynthesis*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism
chemical_list: D001324:Autoantigens; D006182:H-Y Antigen; C028507:H-Y antigen receptor; D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; D011946:Receptors, Antigen; D011948:Receptors, Antigen, T-Cell
keywords: Innate T cells; T-cell development; Thymus