Autocrine IFNγ Controls the Regulatory Function of Lymphoproliferative Double Negative T Cells

Stephen C. Juvet, Mei Han, Ramesh Vanama, Betty Joe, Edward Y. Kim, Fei Linda Zhao, Caroline Jeon, Oyedele Adeyi, Li Zhang

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

TCRαβ+ CD4-CD8-NK- double negative T cells (DN T cells) can act as regulatory T cells to inhibit allograft rejection and autoimmunity. Their role in graft-versus-host disease and mechanisms of suppression remain elusive. In this study, we demonstrate that DN T cells can inhibit CD4+ T cell-mediated GVHD in a semi-allogeneic model of bone marrow transplantation. Furthermore, we present evidence of a novel autocrine IFNγ signaling pathway in Fas-deficient C57BL/6.lpr (B6.lpr) DN T cells. B6.lpr DN T cells lacking IFNγ or its receptor were impaired in their ability to suppress syngeneic CD4+ T cells responding to alloantigen stimulation both in vitro and in vivo. Autocrine IFNγ signaling was required for sustained B6.lpr DN T cell IFNγ secretion in vivo and for upregulation of surface Fas ligand expression during TCR stimulation. Fas ligand (FasL) expression by B6.lpr DN T cells permitted lysis of activated CD4+ T cells and was required for suppression of GVHD. Collectively, our data indicate that DN T cells can inhibit GVHD and that IFNγ plays a critical autocrine role in controlling the regulatory function of B6.lpr DN T cells.

Original languageEnglish (US)
Article numbere47732
JournalPloS one
Volume7
Issue number10
DOIs
StatePublished - Oct 15 2012
Externally publishedYes

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