Autospecific γδ thymocytes that escape negative selection find sanctuary in the intestine

Tesu Lin, Hiroki Yoshida, Goro Matsuzaki, Sarah R. Guehler, Kikuo Nomoto, Terrence A. Barrett, Douglas R. Green

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


αβ or γδ 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 γδ T cells, we have used G8 γδ-T cell transgenic mice, which express a γδ TCR that recognizes the nonpolymorphic MHC class I TL(b) molecule. Here, we demonstrate that negative selection of autospecific γδ 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 γδ 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 γδ 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.

Original languageEnglish
Pages (from-to)1297-1305
Number of pages9
JournalJournal of Clinical Investigation
Issue number9
StatePublished - Nov 1999

ASJC Scopus subject areas

  • Medicine (all)


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