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Antigen-induced unresponsiveness results in altered t cell signaling

Academic Article
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Overview

authors

  • McKay, Dianne
  • Irie, H. Y.
  • Hollander, G.
  • Ferrara, Jlmf
  • Strom, T. B.
  • Li, Yuxing
  • Burakoff, S. J.

publication date

  • December 1999

journal

  • Journal of Immunology  Journal

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-2d) experienced prolonged H-2d cardiac allograft survival, and cells from these mice did not proliferate or make IL-2 in response to alloantigen (H-2d). 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.

subject areas

  • Animals
  • Cells, Cultured
  • Graft Survival
  • Immune Tolerance
  • Injections, Intravenous
  • Isoantigens
  • Lymph Nodes
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phosphorylation
  • Phosphotyrosine
  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • Spleen
  • T-Lymphocytes
  • ras Proteins
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 10586036
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Additional Document Info

start page

  • 6455

end page

  • 6461

volume

  • 163

issue

  • 12

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