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Targeting of a T Cell Agonist Peptide to Lysosomes by DNA Vaccination Induces Tolerance in the Nonobese Diabetic Mouse.
- Source :
-
Journal of Immunology . 4/1/2011, Vol. 186 Issue 7, p4078-4087. 10p. - Publication Year :
- 2011
-
Abstract
- CD4 T cells are crucial effectors in the pathology of type 1 diabetes (T1D). Successful therapeutic interventions for prevention and cure of T1D in humans are still elusive. Recent research efforts have focused on the manipulation of T cells by treatment with DNA. In this paper, we studied the effects of a DNA treatment strategy designed to target antigenic peptides to the lysosomal compartment on a monospecific T cell population termed 2.5mi+ T cells that shares reactivity with the diabetogenic T cell clone BDC-2.5 in the NOD mouse. MHC class II tetramer analysis showed that repeated administrations were necessary to expand 2.5mi+ T cells in vivo. This expansion was independent of Ag presentation by B cells. A single peptide epitope was sufficient to induce protection against T1D, which was not due to Ag-specific T cell anergy. Typical Th2 cytokines such as IL-10 or IL-4 were undetectable in 2.5mi+ T cells, arguing against a mechanism of immune deviation. Instead, the expanded 2.5mi+ T cell population produced IFN-γ similar to 2.5mi+ T cells from naive mice. Protection against T1D by DNA treatment was completely lost in NOD.CD28-/- mice which are largely deficient of natural regulatory T cells (Treg). Although Ag-specific Foxp3+ Treg did not expand in response to DNA treatment, diabetes onset was delayed in Treg-reconstituted and DNA-treated NOD.SCID mice. These observations provide evidence for a Treg-mediated protective mechanism that is independent of the expansion or de novo generation of Ag-specific Treg. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DIABETES
*LABORATORY mice
*T cells
*CD4 antigen
*PEPTIDES
*LYSOSOMES
Subjects
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 186
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 66170123
- Full Text :
- https://doi.org/10.4049/jimmunol.0902395