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Article Dans Une Revue Immunology Letters Année : 2014

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

Résumé

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. 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.
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Dates et versions

hal-01090548 , version 1 (03-12-2014)

Identifiants

Citer

Louis Pérol, Gaëlle H. Martin, Sébastien Maury, José L. Cohen, Eliane Piaggio. Potential limitations of IL-2 administration for the treatment of experimental acute graft-versus-host disease. Immunology Letters, 2014, 162 (2B), pp.173-184. ⟨10.1016/j.imlet.2014.10.027⟩. ⟨hal-01090548⟩
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