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Cutting Edge: Rag deletion in peripheral T cells blocks TCR revision. | LitMetric

AI Article Synopsis

  • Mature CD4(+)Vbeta5(+) T cells can undergo tolerance through deletion or TCR (T Cell Receptor) revision when they recognize an endogenous superantigen.
  • In Vbeta5 transgenic mice, this TCR revision leads to the development of CD4(+)Vbeta5(-)TCRbeta(+) T cells, indicating active rearrangement of TCR genes.
  • The study shows that RAG (Recombination Activating Gene) deletion stops TCR revision in mature T cells, confirming that TCR rearrangement can occur outside the thymus and serves as a tolerance mechanism for peripheral CD4(+) T cells.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929250PMC
http://dx.doi.org/10.4049/jimmunol.1000876DOI Listing

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