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Antigen specificity acquisition of adoptive CD4+ regulatory T cells via acquired peptide-MHC class I complexes.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Aug 15; Vol. 181 (4), pp. 2428-37. - Publication Year :
- 2008
-
Abstract
- The Ag-specific CD4(+) regulatory T (Tr) cells play an important role in immune suppression in autoimmune diseases and antitumor immunity. However, the molecular mechanism for Ag-specificity acquisition of adoptive CD4(+) Tr cells is unclear. In this study, we generated IL-10- and IFN-gamma-expressing type 1 CD4(+) Tr (Tr1) cells by stimulation of transgenic OT II mouse-derived naive CD4(+) T cells with IL-10-expressing adenovirus (AdV(IL-10))-transfected and OVA-pulsed dendritic cells (DC(OVA/IL-10)). We demonstrated that both in vitro and in vivo DC(OVA/IL-10)-stimulated CD4(+) Tr1 cells acquired OVA peptide MHC class (pMHC) I which targets CD4(+) Tr1 cells suppressive effect via an IL-10-mediated mechanism onto CD8(+) T cells, leading to an enhanced suppression of DC(OVA)-induced CD8(+) T cell responses and antitumor immunity against OVA-expressing murine B16 melanoma cells by approximately 700% relative to analogous CD4(+) Tr1 cells without acquired pMHC I. Interestingly, the nonspecific CD4(+)25(+) Tr cells can also become OVA Ag specific and more immunosuppressive in inhibition of OVA-specific CD8(+) T cell responses and antitumor immunity after uptake of DC(OVA)-released exosomal pMHC I complexes. Taken together, the Ag-specificity acquisition of CD4(+) Tr cells via acquiring DC's pMHC I may be an important mean in augmenting CD4(+) Tr cell suppression.
- Subjects :
- Animals
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Cell Differentiation immunology
Cross-Priming immunology
Dendritic Cells immunology
Female
Graft vs Host Disease immunology
H-2 Antigens immunology
H-Y Antigen administration & dosage
H-Y Antigen metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Minor Histocompatibility Antigens
Peptides administration & dosage
Peptides metabolism
Proteins immunology
Proteins metabolism
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Time Factors
Adoptive Transfer
Epitopes, T-Lymphocyte immunology
Epitopes, T-Lymphocyte metabolism
H-2 Antigens metabolism
H-Y Antigen immunology
Models, Immunological
Peptides immunology
T-Lymphocytes, Regulatory transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 181
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 18684933
- Full Text :
- https://doi.org/10.4049/jimmunol.181.4.2428