Antigen-induced unresponsiveness results in altered T cell signaling

Dianne B. McKay, Hanna Y. Irie, Georg Hollander, James L.M.F. Ferrara, Terry B. Strom, Yongsheng Li, Steven J. Burakoff

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Pretransplant exposure to allogeneic lymphocytes can result in donor- specific unresponsiveness and prolonged allograft survival. Intracellular signaling events have been described in anergic T cell clones, but the biochemical events underlying in vivo induced unresponsiveness have not been studied in detail. We employed a TCR transgenic mouse, bearing the 2C TCR, providing adequate numbers of homogenous peripheral T cells to study biochemical aspects of T cell unresponsiveness in vivo. 2C mice exposed to semiallogeneic lymphocytes (H-2b x H-2(d)) experienced prolonged H-2(d) cardiac allograft survival, and cells from these mice did not proliferate or make IL-2 in response to alloantigen (H-2(d)). Importantly, there were marked differences in TCR-associated tyrosine phosphorylation activation patterns. The targets for the unresponsive state appear to be diminished Lck activation and absent ZAP-70 and LAT (linker for activation of T cells) phosphorylation. Our study demonstrates that Ag-induced tolerance in vivo is accompanied by altered early TCR-mediated signaling events.

Original languageEnglish
Pages (from-to)6455-6461
Number of pages7
JournalJournal of Immunology
Volume163
Issue number12
StatePublished - 1999
Externally publishedYes

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