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Blood. 2012 Apr 19;119(16):3844-53. doi: 10.1182/blood-2011-10-384057. Epub 2011 Nov 18.

Induction of acute GVHD by sex-mismatched H-Y antigens in the absence of functional radiosensitive host hematopoietic-derived antigen-presenting cells.

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1
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, USA.

Abstract

It is currently thought that acute GVHD cannot be elicited in the absence of Ag presentation by radiosensitive host hematopoietic-derived APCs after allogeneic BM transplantation. Because clinical data suggest that sex-mismatched H-Y Ags may be important minor histocompatibility Ags for GVH responses, we directly tested their relevance and ability to initiate GVHD when presented by either the hematopoietic- (host or donor) or the nonhematopoietic-derived APCs. H-Y minor Ag incompatibility elicited both CD4(+) and CD8(+) T-cell driven GVHD lethality. Studies with various well-established BM chimera recipients, in contrast to the current views, have reported that in the absence of functional radiosensitive host hematopoietic-derived APCs, H-Y Ag presentation by either the donor hematopoietic-derived or the host nonhematopoietic-derived APCs is sufficient for inducing GVHD. Our data further suggest that infusion of sufficient numbers of alloreactive donor T cells will induce GVHD in the absence of radiosensitive host hematopoietic-derived APCs.

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PMID:
22101894
PMCID:
PMC3335388
DOI:
10.1182/blood-2011-10-384057
[Indexed for MEDLINE]
Free PMC Article
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