Tr1 and naturally occurring regulatory T cells induce IgG4 in B cells through GITR/GITR-L interaction, IL-10 and TGF-beta.
Eur J Immunol
; 38(11): 3101-13, 2008 Nov.
Article
em En
| MEDLINE
| ID: mdl-18924213
ABSTRACT
Regulatory T cells exert their function through the modulation of both T and B cell responses. Our previous studies demonstrated that IL-10-producing Treg (Tr1) can induce B cells to secrete IgG4 in a cell-contact-dependent manner. The benefit of such non-inflammatory B-cell responses is apparent in the hyporesponsive state of patients with helminth infections such as Onchocerciasis. Here, we investigated the mechanisms involved to induce IgG4, within BTr-cell co-cultures, using IL-10-producing tetanus-toxoid-specific regulatory T cell lines and clones (Tr-TCC) from human PBMC. During the generation process, we found that increasing Foxp3 levels in regulatory T cell lines correlated with their ability to induce IgG4 in B cells. Using Tr-TCC, we found that blocking glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) molecules selectively prevented IgG4 production as did neutralizing Ab to glucocorticoid-induced tumour necrosis factor receptor-related protein ligand (GITR-L), IL-10 and TGF-beta. Furthermore, the prevention of IgG4 induction by anti-GITR Ab was reversed by excess rIL-10 but not rTGF-beta. In contrast, anti-ICOS and anti-CTLA-4 Abs had no effect. When compared with Tr-TCC, freshly isolated CD4+CD25+ T cells, but not effector T cell populations, induced low levels of IgG4, which were also blocked by anti-GITR and anti-GITR-L Ab. Thus, the mechanism of IgG4 induction by regulatory cells involves GITR-GITR-L interactions, IL-10 and TGF-beta.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina G
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Linfócitos B
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Fator de Crescimento Transformador beta
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Interleucina-10
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Receptores de Fator de Crescimento Neural
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Linfócitos T Reguladores
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Receptores do Fator de Necrose Tumoral
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Fatores de Necrose Tumoral
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article