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Transplantation Tolerance to a Single Noninherited MHC Class I Maternal Alloantigen Studied in a TCR-Transgenic Mouse Model.
- Source :
-
Journal of Immunology . 2/1/2011, Vol. 186 Issue 3, p1442-1449. 8p. - Publication Year :
- 2011
-
Abstract
- The mechanisms underlying tolerance to noninherited maternal Ags (NIMA) are not fully understood. In this study, we designed a double-transgenic model in which all the offspring's CD8+ T cells corresponded to a single clone recognizing the Kb MHC class I protein. In contrast, the mother and the father of the offspring differed by the expression of a single Ag, Kb, that served as NIMA. We investigated the influence of NIMA exposure on the offspring thymic T cell selection during ontogeny and on its peripheral T cell response during adulthood. We observed that anti-Kb thymocytes were exposed to NIMA and became activated during fetal life but were not deleted. Strikingly, adult mice exposed to NIMA accepted permanently Kb+ heart allografts despite the presence of normal levels of anti-Kb TCR transgenic T cells. Transplant tolerance was associated with a lack of a proinflammatory alloreactive T cell response and an activation/expansion of T cells producing IL-4 and IL-10. In addition, we observed that tolerance to NIMA Kb was abrogated via depletion of CD4+ but not CD8+ T cells and could be transferred to naive nonexposed mice via adoptive transfer of CD4+CD25high T cell expressing Foxp3 isolated from NIMA mice. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 186
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 65957922
- Full Text :
- https://doi.org/10.4049/jimmunol.1003023