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Th17 Alloimmunity Prevents Neonatal Establishment of Lymphoid Chimerism in IL-4-Deprived Mice

Authors :
Debock, I.
Delbauve, S.
Dubois, A.
Pétein, M.
Leo, O.
Goldman, M.
Flamand, V.
Source :
American journal of transplantation; January 2012, Vol. 12 Issue: 1 p81-89, 9p
Publication Year :
2012

Abstract

Immune responses in newborn mice are known to be biased toward the helper type 2 phenotype. This may account for their propensity to develop tolerance. Herein, we evaluated the effects of IL-4 deprivation on CD4+T-cell activities elicited by neonatal exposure to allogeneic spleen cells. We showed that chimerism, Th2-type polarization and pathology, as well as skin allograft acceptance were inhibited in BALB/c mice immunized at birth with (A/J x BALB/c) F1spleen cells upon in vivoIL-4 neutralization. While IL-4 neutralization inhibited the development of Th2 cells in this model, it led to the accumulation of IL-17A, IL-17F, IL-22, IL-6 and RORγt mRNA in the spleen or graft tissues. Moreover, IL-4 deprivation led to the differentiation of donor-specific Th17 cells with a concomitant Th1 response characterized by IFN-γ production. The Th17-type response emerging in IL-4-deprived mice was found to mediate both intragraft neutrophil infiltration and the abrogation of B-cell chimerism. Neutralization of this Th17 response failed however to restore functional skin graft acceptance. Collectively, our observations indicate that the neonatal Th2 response opposes the development of Th17 cells, and that Th17 cells are responsible for controlling lymphoid chimerism in mice neonatally injected with semiallogeneic cells.

Details

Language :
English
ISSN :
16006135 and 16006143
Volume :
12
Issue :
1
Database :
Supplemental Index
Journal :
American journal of transplantation
Publication Type :
Periodical
Accession number :
ejs62082692
Full Text :
https://doi.org/10.1111/j.1600-6143.2011.03778.x