Novel CD8+ Treg suppress EAE by TGF-beta- and IFN-gamma-dependent mechanisms.
Eur J Immunol
; 39(12): 3423-35, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-19768696
ABSTRACT
Although CD8+ Treg-mediated suppression has been described, CD8+ Treg remain poorly characterized. Here we identify a novel subset of CD8+ Treg that express latency-associated peptide (LAP) on their cell surface (CD8+LAP+ cells) and exhibit regulatory activity in vitro and in vivo. Only a small fraction of CD8+LAP+ cells express Foxp3 or CD25, although the expression levels of Foxp3 for these cells are higher than their LAP- counterparts. In addition to TGF-beta, CD8+LAP+ cells produce IFN-gamma, and these cells suppress EAE that is dependent on both TGF-beta and IFN-gamma. In an adoptive co-transfer model, CD8+LAP+ cells suppress myelin oligodendrocyte glycoprotein (MOG)-specific immune responses by inducing or expanding Foxp3+ cells and by inhibiting proliferation and IFN-gamma production in vivo. Furthermore, in vivo neutralization of IFN-gamma and studies with IFN-gamma-deficient mice demonstrate an important role for IFN-gamma production in the function of CD8+LAP+ cells. Our findings identify the underlying mechanisms that account for the immunoregulatory activity of CD8+ T cells and suggest that induction or amplification of CD8+LAP+ cells may be a therapeutic strategy to help control autoimmune processes.
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Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta
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Interferon gama
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Linfócitos T Reguladores
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Encefalomielite Autoimune Experimental
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article