Curative and protective effects of IL-10 in experimental autoimmune thyroiditis (EAT). Evidence for IL-10-enhanced cell death in EAT.
We studied the effects of in vivo administration of rhIL-10 in two models of experimental autoimmune thyroiditis (EAT): 1)-in EAT induced by injection of mTg emulsified in adjuvant, and 2) in EAT induced by adoptive transfer of mTg-specific T lymphocytes. Furthermore, we tried to assess both the protective and curative potential of IL-10 in EAT, by administering rhIL-10 either at the time of priming and challenge with mTg, or only at the time of challenge. We demonstrated that proliferative and cytotoxic responses of splenic cells to mTg were markedly reduced by in vivo rhIL-10 treatment. Cell surface marker studies revealed a 40 to 45% reduction in CD4+ and in CD8+ lymphoblastoid spleen cells from mice treated with rhIL-10 either in the early or in the late EAT. The severity of EAT was significantly reduced in mice treated with high-dose rhIL-10, whereas levels of autoantibodies to mTg were not altered. Furthermore, when analyzing purified T lymphocytes from rhIL-10-treated animals, an increase of cells undergoing apoptotic cell death became evident in the rhIL-10 treated group, as compared with controls. This IL-10-mediated enhancement of activation-induced cell death critically depended on the applied therapeutic dose of rhIL-10. Thus, IL-10 exerts beneficial effects on the development and course of EAT through a mechanism that could imply an IL-10-mediated enhancement of activation-induced cell death in T lymphocytes, findings that call for considering IL-10 in the immunotherapy of early-phase and likewise of already established autoimmune thyroiditis.
Mignon-Godefroy
K
K
INSERM Unit 283, René Descartes University, Cochin Hospital, Paris, France.
Rott
O
O
Brazillet
M P
MP
Charreire
J
J
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D016219:Immunotherapy, Adoptive; D016753:Interleukin-10 / Q000494:pharmacology* / Q000627:therapeutic use; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*
D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D016753:Interleukin-10