TCR revision generates functional CD4+ T cells.
CD4(+)Vβ5(+) peripheral T cells in C57BL/6 mice respond to encounter with a peripherally expressed endogenous superantigen by undergoing either deletion or TCR revision. In this latter process, cells lose surface Vβ5 expression and undergo RAG-dependent rearrangement of endogenous TCRβ genes, driving surface expression of novel TCRs. Although postrevision CD4(+)Vβ5(-)TCRβ(+) T cells accumulate with age in Vβ5 transgenic mice and bear a diverse TCR Vβ repertoire, it is unknown whether they respond to homeostatic and antigenic stimuli and thus may benefit the host. We demonstrate in this study that postrevision cells are functional. These cells have a high rate of steady-state homeostatic proliferation in situ, and they undergo extensive MHC class II-dependent lymphopenia-induced proliferation. Importantly, postrevision cells do not proliferate in response to the tolerizing superantigen, implicating TCR revision as a mechanism of tolerance induction and demonstrating that TCR-dependent activation of postrevision cells is not driven by the transgene-encoded receptor. Postrevision cells proliferate extensively to commensal bacterial Ags and can generate I-A(b)-restricted responses to Ag by producing IFN-γ following Listeria monocytogenes challenge. These data show that rescued postrevision T cells are responsive to homeostatic signals and recognize self- and foreign peptides in the context of self-MHC and are thus useful to the host.
Hale
J Scott
JS
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Wubeshet
Maramawit
M
Fink
Pamela J
PJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D007108:Immune Tolerance / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell