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

T Toubai, I Tawara, Y Sun, C Liu… - Blood, The Journal …, 2012 - ashpublications.org
T Toubai, I Tawara, Y Sun, C Liu, E Nieves, R Evers, T Friedman, R Korngold, P Reddy
Blood, The Journal of the American Society of Hematology, 2012ashpublications.org
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 HY 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. HY minor Ag incompatibility elicited both CD4+ and CD8+ …
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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