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Tr1 and naturally occurring regulatory T cells induce IgG4 in B cells through GITR/GITR-L interaction, IL-10 and TGF-beta.
- Source :
-
European journal of immunology [Eur J Immunol] 2008 Nov; Vol. 38 (11), pp. 3101-13. - Publication Year :
- 2008
-
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 B:Tr-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.
- Subjects :
- Antigens, CD physiology
CTLA-4 Antigen
Cell Line
Forkhead Transcription Factors analysis
Forkhead Transcription Factors physiology
Glucocorticoid-Induced TNFR-Related Protein
Humans
Immunologic Memory
B-Lymphocytes immunology
Immunoglobulin G biosynthesis
Interleukin-10 physiology
Receptors, Nerve Growth Factor physiology
Receptors, Tumor Necrosis Factor physiology
T-Lymphocytes, Regulatory immunology
Transforming Growth Factor beta physiology
Tumor Necrosis Factors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2980
- Volume :
- 38
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 18924213
- Full Text :
- https://doi.org/10.1002/eji.200838193