Impaired signaling in alloantigen-specific CD8+ T cells tolerized in vivo: employing a model of Ld-specific TCR transgenic mice transplanted with allogenic hearts under the cover of a short-term rapamycin treatment.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

J Immunol. 1996 Nov 15;157(10):4297-308. Unique Identifier : AIDSLINE MED/97064184
Chen H; Luo H; Xu D; Loh DY; Daloze PM; Veillette A; Qi S; Wu J; Louis-Charles Simard Research Center, Notre-Dame Hospital,; University of Montreal, Canada.

Abstract: Peripheral tolerance of T cells is necessary because thymic deletion is not complete, and tissue-specific Ags exist outside the thymus. We have reported that persistent Ag is required to maintain peripheral tolerance in vivo. We suspect that the TCR signaling pathway in in vivo tolerized cells is compromised due to continuous exposure to the Ags. In this study, the TCR signaling events in these cells were investigated using TCR transgenic mice (2C mice) whose T cells are predominantly Ld alloantigen-specific CD8 cells. The 2C mice were thymectomized and then rendered tolerant to Ld Ag by allogenic heart transplantation plus short-term treatment with rapamycin. We found that 1) the in vivo tolerized CD8 cells have compromised intracellular Ca2+ flux upon mitogen stimulation; and 2) their cellular tyrosine proteins fail to be phosphorylated properly upon TCR cross-linking. These results indicate that the signaling pathway in the in vivo tolerized CD8 cells is indeed defective. We also found that 1) the tolerized CD8 cells have no characteristic surface markers; and 2) the allograft is probably the place where the rejection response is initiated according to the appearance of an early activation marker of T cells on graft-infiltrating cells.

Keywords: src-Family Kinases/ANALYSIS Animal CD8-Positive T-Lymphocytes/DRUG EFFECTS/ENZYMOLOGY/*IMMUNOLOGY H-2 Antigens/GENETICS/*IMMUNOLOGY Heart Transplantation/*IMMUNOLOGY Immune Tolerance/*DRUG EFFECTS Immunosuppressive Agents/PHARMACOLOGY Isoantigens/*IMMUNOLOGY Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred Strains Mice, Transgenic Models, Immunological Polyenes/*PHARMACOLOGY Protein-Tyrosine Kinase/ANALYSIS Proto-Oncogene Proteins/ANALYSIS Receptors, Antigen, T-Cell/*IMMUNOLOGY Signal Transduction/*DRUG EFFECTS/*IMMUNOLOGY Support, Non-U.S. Gov't Transplantation, Homologous JOURNAL ARTICLE
970228
M9721864

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