TCR Revision Generates Functional CD4+ T Cells

CD4(+)V beta 5(+) 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 V beta 5 expression and undergo RAG-dependent rearrangement of endogenous TCR beta genes, driving surface expression of novel TCRs. Although postrevision CD4(+)V beta 5(-)TCR beta(+) T cells accumulate with age in V beta 5 transgenic mice and bear a diverse TCR V beta 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-gamma 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. The Journal of Immunology, 2010, 185: 6528-6534.