title: Autospecific gammadelta thymocytes that escape negative selection find sanctuary in the intestine.
abstract: alphabeta or gammadelta thymocytes whose T-cell receptors (TCRs) recognize endogenously expressed antigens (Ag) are autospecific and, thus, potentially self-reactive. In the thymus, such T cells are eliminated during T-cell development through a process known as negative selection. As a model of negative selection of gammadelta T cells, we have used G8 gammadelta-T cell transgenic mice, which express a gammadelta TCR that recognizes the nonpolymorphic MHC class I TL(b) molecule. Here, we demonstrate that negative selection of autospecific gammadelta T cells is almost complete in the adult thymus but is markedly attenuated in the neonatal thymus. A consequence of this attenuated negative selection is that potentially self-reactive gammadelta thymocytes are allowed to escape negative selection, undergo extrathymic differentiation, and find sanctuary in the intestinal epithelium. Interestingly, the ability of these potentially self-reactive gammadelta T cells to find sanctuary requires both the intestinal epithelial environment and the extrathymic presence of the self-Ag. The implications of these findings on the development and persistence of autoreactive T cells in autoimmune disease are discussed.
authors.affiliation: Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
authors.forename: T
authors.initials: T
authors.lastname: Lin
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: G
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: S R
authors.initials: SR
authors.lastname: Guehler
authors.forename: K
authors.initials: K
authors.lastname: Nomoto
authors.forename: T A
authors.initials: TA
authors.lastname: Barrett
authors.forename: D R
authors.initials: DR
authors.lastname: Green
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division; D002465:Cell Movement; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D019169:Jurkat Cells; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000254:growth & development / Q000276:immunology
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta