Transplantation tolerance induced by intranasal administration of HY peptides
Chai, Jian-Guo, James, Edward, Dewchand, Hamlata, Simpson, Elizabeth and Scott, Diane (2004) Transplantation tolerance induced by intranasal administration of HY peptides. Blood, 103, (10), 3951-3959. (doi:10.1182/blood-2003-11-3763).
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Induction of antigen-specific tolerance to transplantation antigens is desirable to control host-versus-graft and graft-versus-host reactions. Following molecular identification of a set of minor histocompatibility (H) antigens, we have used selected HY peptide epitopes for this purpose. Intranasal administration of individual major histocompatibility complex (MHC) class II-restricted HY peptides induces indefinite survival of syngeneic male skin grafts and allows engraftment of male bone marrow.
Tolerance involves linked suppression to additional HY epitopes on test grafts. Long-term tolerance also requires suppression of emerging thymic emigrants. It does not involve deletion. HY peptide-specific CD4(+) and CD8(+) T cells expand on re-exposure to male antigen; these expansions are smaller in tolerant than control mice and fewer HY-specific cells from tolerant females secrete interferon gamma and interleukin 10 (IL-10). Significantly, CD4(+) cells from peptide-pretreated females fail to make IL-2 responses to cognate peptide, limiting expansion of the HY-specific CD8(+) populations that can cause graft rejection.
Consistent with this, tolerance induction by HY peptide is abrogated by coadministration of lipopolysaccharide. IL-10 does not appear to be critically involved because tolerance is inducible in IL-10-deficient mice. Adoptive transfer of tolerance into naive neonatal recipients by splenocytes from long-term tolerant donors provides evidence for involvement of regulatory cells.
|Digital Object Identifier (DOI):||doi:10.1182/blood-2003-11-3763|
|Subjects:||Q Science > QP Physiology
Q Science > QR Microbiology
|Divisions :||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|Accepted Date and Publication Date:||
|Date Deposited:||07 Jul 2006|
|Last Modified:||31 Mar 2016 12:11|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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