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. 2014 Dec;162(2 Pt B):173-84.
doi: 10.1016/j.imlet.2014.10.027. Epub 2014 Nov 5.

Potential limitations of IL-2 administration for the treatment of experimental acute graft-versus-host disease

Louis Pérol  1 , Gaëlle H Martin  2 , Sébastien Maury  3 , José L Cohen  4 , Eliane Piaggio  5
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Potential limitations of IL-2 administration for the treatment of experimental acute graft-versus-host disease

Louis Pérol et al. Immunol Lett. 2014 Dec.

Abstract

Low-dose IL-2 administration can control autoimmunity by specifically activating CD4(+) Foxp3(+) regulatory T cells (Tregs). Here, we studied IL-2-based immunotherapy in experimental graft-versus-host disease (GVHD). IL-2 administration to donor mice induced a dose-dependent expansion of Tregs in the graft but was insufficient to control GVHD. IL-2 administration to allogeneic-grafted recipient mice activated T-conventional cells (Tcons) and did not prevent GVHD. This loss of IL-2 selectivity toward Tregs was explained by an IL-2-induced increase in the IL-2 receptor α-chain expression on Tcons VSports手机版. Finally, in xeno-GVHD generated by human PBMCs transplanted into immunodeficient mice, low-dose IL-2 increased Treg frequencies but did neither control pro-inflammatory cytokine production by pathogenic Tcons, nor prevented GVHD. Furthermore, combination of low-dose IL-2 with rapamycin was ineffective in this model. Our results indicate that limitations on the use of IL-2 during acute GVHD are likely due to the massive activation of the allogeneic T cells unique to this setting. .

Keywords: Bone marrow transplantation; Graft-vs-host disease; Immunotherapy; Interleukin-2; Regulatory T cell V体育安卓版. .

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