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Immunol Lett. 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.

Author information

1
INSERM U932, 26 rue d'Ulm, 75005 Paris, France; Institut Curie, Section Recherche, 26 rue d'Ulm, 75005 Paris, France; Université Pierre et Marie Curie Paris 06, UMR7211, Immunology-Immunopathology-Immunotherapy (I3), F-75013 Paris, France; CNRS, UMR7211, I3, F-75013 Paris, France.
2
Université Paris-Est Créteil, Faculté de médecine, Créteil F-94010, France; INSERM U 955, Institut Mondor de Recherche Biomédicale (IMRB), Créteil F-94010, France.
3
Université Paris-Est Créteil, Faculté de médecine, Créteil F-94010, France; INSERM U 955, Institut Mondor de Recherche Biomédicale (IMRB), Créteil F-94010, France; AP-HP, Groupe Hospitalier Henri-Mondor Albert-Chenevier, CIC-BT-504, Créteil, France.
4
Université Paris-Est Créteil, Faculté de médecine, Créteil F-94010, France; INSERM U 955, Institut Mondor de Recherche Biomédicale (IMRB), Créteil F-94010, France; AP-HP, Groupe Hospitalier Henri-Mondor Albert-Chenevier, CIC-BT-504, Créteil, France. Electronic address: jose.cohen@inserm.fr.
5
INSERM U932, 26 rue d'Ulm, 75005 Paris, France; Institut Curie, Section Recherche, 26 rue d'Ulm, 75005 Paris, France; Université Pierre et Marie Curie Paris 06, UMR7211, Immunology-Immunopathology-Immunotherapy (I3), F-75013 Paris, France; CNRS, UMR7211, I3, F-75013 Paris, France; INSERM Center of Clinical Investigation (CIC-BT-507), 75005 Paris, France. Electronic address: eliane.piaggio@yahoo.com.

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. 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

PMID:
25445496
DOI:
10.1016/j.imlet.2014.10.027
[Indexed for MEDLINE]

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