Different costimulatory and growth factor requirements for CD4+ and CD8+ T cell-mediated rejection

Minh Diem Vu, Farhana Amanullah, Yongsheng Li, Gulcin Demirci, Mohamed H. Sayegh, Xian Chang Li

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Costimulatory signals and growth factor signals play a key role in commanding T cell activation and T cell effector function. However, how costimulatory signals and growth factor signals interact and integrate into the activation program of CD4+ and CD8+ T cells during the allograft response remains poorly defined. In the present study we found that either CD4- or CD8-deficient mice can vigorously reject the skin allografts. Blocking rapamycin-sensitive growth factor signals produced long term skin allograft survival in CD4-deficient mice (mean survival time, >120 days), but not in CD8-deficient mice (mean survival time, 20 days). Analysis of CFSE-labeled cells proliferating in the allogeneic hosts revealed that clonal expansion of CD4+ T cells in vivo was more resistant to growth factor blockade than that of CD8+ T cells. However, blockade or genetic absence of CD28/CD154 costimulatory molecules rendered CD4+ T cell-mediated rejection sensitive to rapamycin, and long term skin allograft survival can be readily induced by rapamycin in the absence of CD28/CD154 signals (>100 days). Furthermore, blocking OX40 costimulation induced long term skin allograft survival in CD4-deficient mice and CD8-deficient mice when both CD28 and CD154 were transiently blocked. We conclude that CD4+ and CD8+ T cells exhibit distinct sensitivity to growth factor blockade in transplant rejection, and CD28/CD154-independent rejection is sensitive to rapamycin and appears to be supported by OX40 costimulation.

Original languageEnglish (US)
Pages (from-to)214-221
Number of pages8
JournalJournal of Immunology
Volume173
Issue number1
DOIs
StatePublished - Jul 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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