Type I-IFNs control GVHD and GVL responses after transplantation

Robb, Renee J., Kreijveld, Ellen, Kuns, Rachel D., Wilson, Yana A., Olver, Stuart D., Don, Alistair L. J., Raffelt, Neil C., De Weerd, Nicole A., Lineburg, Katie E., Varelias, Antiopi, Markey, Kate A., Koyama, Motoko, Clouston, Andrew D., Hertzog, Paul J., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2011) Type I-IFNs control GVHD and GVL responses after transplantation. Blood, 118 12: 3399-3409. doi:10.1182/blood-2010-12-325746

Author Robb, Renee J.
Kreijveld, Ellen
Kuns, Rachel D.
Wilson, Yana A.
Olver, Stuart D.
Don, Alistair L. J.
Raffelt, Neil C.
De Weerd, Nicole A.
Lineburg, Katie E.
Varelias, Antiopi
Markey, Kate A.
Koyama, Motoko
Clouston, Andrew D.
Hertzog, Paul J.
MacDonald, Kelli P. A.
Hill, Geoffrey R.
Title Type I-IFNs control GVHD and GVL responses after transplantation
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2011-09-22
Sub-type Article (original research)
DOI 10.1182/blood-2010-12-325746
Volume 118
Issue 12
Start page 3399
End page 3409
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Collection year 2012
Language eng
Formatted abstract
Although the effects of type II-IFN (IFN-γ) on GVHD and leukemia relapse are well studied, the effects of type I-interferon (type I-IFN, IFN-α/β) remain unclear. We investigated this using type I-IFN receptor-deficient mice and exogenous IFN-α administration in established models of GVHD and GVL. Type I-IFN signaling in host tissue prevented severe colon-targeted GVHD in CD4-dependent models of GVHD directed toward either major histocompatibility antigens or multiple minor histocompatibility antigens. This protection was the result of suppression of donor CD4+ T-cell proliferation and differentiation. Studies in chimeric recipients demonstrated this was due to type I-IFN signaling in hematopoietic tissue. Consistent with this finding, administration of IFN-α during conditioning inhibited donor CD4+ proliferation and differentiation. In contrast, CD8-dependent GVHD and GVL effects were enhanced when type I-IFN signaling was intact in the host or donor, respectively. This finding reflected the ability of type I-IFN to both sensitize host target tissue/leukemia to cell-mediated cytotoxicity and augment donor CTL function. These data confirm that type I-IFN plays an important role in defining the balance of GVHD and GVL responses and suggests that administration of the cytokine after BM transplantation could be studied prospectively in patients at high risk of relapse.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
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