Both perform and Fas ligand are required for the regulation of alloreactive CD8 + T cells during acute graft-versus-host disease

Yoshinobu Maeda, Robert B. Levy, Pavan Reddy, Chen Liu, Shawn G. Clouthier, Takanori Teshima, James L.M. Ferrara

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Fas ligand (Fast) and perform pathways not only are the major mechanisms of T cell-mediated cytotoxicity but also are involved in homeostatic regulation of these T cells. In the present study, we tested whether CD8 + donor T cells that are deficient in both perform and FasL (cytotoxic double deficient [cdd]) could induce graft-versus-host disease (GVHD) in a major histocompatibility complex class I-mismatched lethally irradiated murine model. Interestingly, recipients of cdd CD8 + T cells demonstrated significantly greater serum levels of interferon gamma and tumor necrosis factor alpha and histopathologic damage from GVHD than wild-type (wt) T cells on day 30 after allogeneic bone marrow transplantation (P <.05). Wt and either perforin-deficient or FasL-deficient CD8 + T cells expanded early after transplantation followed by a contraction phase in which the majority of expanded CD8 + T cells were eliminated. In contrast, cdd CD8 + T cells exhib ited prolonged expansion and reduced apoptosis to alloantigen stimulation in vivo and in vitro. Together these results suggest that donor cdd CD8 + T cells expand continuously and cause lethal GVHD, and that both perform and FasL are required for the contraction of alloreactive CD8 + T cells.

Original languageEnglish (US)
Pages (from-to)2023-2027
Number of pages5
JournalBlood
Volume105
Issue number5
DOIs
StatePublished - Mar 1 2005

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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