First Author | Hale JS | Year | 2010 |
Journal | J Immunol | Volume | 184 |
Issue | 11 | Pages | 5964-8 |
PubMed ID | 20435935 | Mgi Jnum | J:161222 |
Mgi Id | MGI:4457812 | Doi | 10.4049/jimmunol.1000876 |
Citation | Hale JS, et al. (2010) Cutting Edge: Rag deletion in peripheral T cells blocks TCR revision. J Immunol 184(11):5964-8 |
abstractText | Mature CD4(+)Vbeta5(+) T cells that recognize a peripherally expressed endogenous superantigen are tolerized either by deletion or TCR revision. In Vbeta5 transgenic mice, this latter tolerance pathway results in the appearance of CD4(+)Vbeta5(-)TCRbeta(+) T cells, coinciding with Rag1, Rag2, and TdT expression and the accumulation of V(beta)-DJ(beta) recombination intermediates in peripheral CD4(+) T cells. Because postthymic RAG-dependent TCR rearrangement has remained controversial, we sought to definitively determine whether TCR revision is an extrathymic process that occurs in mature peripheral T cells. We show in this study that Rag deletion in post-positive selection T cells in Vbeta5 transgenic mice blocks TCR revision in vivo and that mature peripheral T cells sorted to remove cells bearing endogenous TCRbeta-chains can express newly generated TCRbeta molecules in adoptive hosts. These findings unambiguously demonstrate postthymic, RAG-dependent TCR rearrangement and define TCR revision as a tolerance pathway that targets mature peripheral CD4(+) T cells. |