RESUMO
IL-10 is a key immune-regulatory cytokine, and its gene polymorphisms correlate with severity of clinical GVHD. IL-10 is made by a variety of donor and host cells, but the functional relevance of its source and its role in the biology of acute GVHD are not well understood. We used preclinical models to examine the relevance of IL-10(-/-) in donor and host cellular subsets on the severity of GVHD. IL-10(-/-) in host tissues or in the donor grafts did not alter donor Teff-mediated severity of GVHD. Furthermore, neither host-derived nor donor Teff-derived IL-10 was required for regulation of GVHD by WT CD4(+)CD25(+) donor Tregs. By contrast, Treg-derived IL-10, although not obligatory, was necessary for optimal reduction of GVHD by mature donor Tregs. Importantly, IL-10 from donor BM grafts was also critical for optimal donor Treg-mediated suppression of GVHD. Together, these data suggest that IL-10 does not contribute to the induction of GVHD severity by the Teffs. However, donor BM graft and Treg-derived IL-10 are important for donor Treg-mediated suppression of GVHD.
Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/imunologia , Interleucina-10/imunologia , Linfócitos T Reguladores/imunologia , Animais , Modelos Animais de Doenças , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/patologia , Humanos , Interleucina-10/biossíntese , Interleucina-10/genética , Camundongos , Camundongos Knockout , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Transplante HomólogoRESUMO
Host hematopoietic-derived antigen-presenting cells are important for induction of graft-versus-host disease (GVHD). The relative importance of various subsets of hematopoietic-derived antigen-presenting cells is not well understood. Recent data suggest that basophils can function as antigen-presenting cells and induce T helper 2 (Th2) lymphocyte responses. We investigated the role of host basophils in the induction of donor T cell responses and GVHD after allogeneic bone marrow transplantation. Elimination of host basophils did not alter the severity of GVHD-induced mortality across multiple clinically relevant models of allogeneic bone marrow transplantation. Furthermore, induction of donor T cell proliferation and Th2 polarization was not altered significantly after depletion of host basophils. Our results demonstrate that, in contrast to their role in inducing Th2 responses in certain contexts, basophils are dispensable for the induction of donor Th2 responses and for the severity of GVHD.
