Cognate CD4(+) help elicited by resting dendritic cells does not impair the induction of peripheral tolerance in CD8(+) T cells
- Author(s)
- Steptoe, RJ; Ritchie, JM; Wilson, NS; Villadangos, JA; Lew, AM; Harrison, LC;
- Details
- Publication Year 2007-02-15,Volume 178,Issue #4,Page 2094-2103
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Peripheral tolerance is required to prevent autoimmune tissue destruction by self-reactive T cells that escape negative selection in the thymus. One mechanism of peripheral tolerance in CD8(+) T cells is their activation by resting dendritic cells (DC). In contrast, DC can be "licensed" by CD4(+) T cells to induce cytotoxic function in CD8(+) T cells. The question that then arises, whether CD4(+) T cell help could impair peripheral tolerance induction in self-reactive CD8(+) T cells, has not been addressed. In this study we show that CD4(+) T cell activation by resting DC results in helper function that transiently promotes the expansion and differentiation of cognate CD8(+) T cells. However, both the CD4(+) and CD8(+) T cell populations ultimately undergo partial deletion and acquire Ag unresponsiveness, disabling their ability to destroy OVA-expressing pancreatic beta cells and cause diabetes. Thus, effective peripheral tolerance can be induced by resting DC in the presence of CD4(+) and CD8(+) T cells with specificity for the same Ag. The Journal of Immunology, 2007, 178: 2094-2103.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- RESTRICTED CROSS-PRESENTATION; MYELIN BASIC-PROTEIN; IN-VIVO; ANTIGEN PRESENTATION; SELF-ANTIGENS; POSITIVE SELECTION; FLOW-CYTOMETRY; RESPONSES; COMPLEX; MICE
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- Refer to copyright notice on published article.
Creation Date: 2007-02-15 12:00:00