![]() As acute GVHD subside into chronic GVHD, alloreactive pathogenic memory T, especially CD4 + memory T cells, that can cross-react with donor APCs become autoreactive CD4 + T cells and gather in the GVHD target tissue. Damage of bone marrow microenvironment results in increased production of autoreactive B cells and reduced production of tolerogenic plasmacytoid dendritic cells (pDCs). ![]() Damage of thymic medullary epithelial cells (mTECs) leads to decreased generation of thymic Tregs (tTreg) cells and increased release of autoreactive T cells that are cross-reactive with donor antigen-MHC complex and host antigen-MHC complex. The Th1/Tc1 cells infiltrate GVHD target tissues including thymus and bone marrow. At the same time, some of the autoreactive CD4 + T cells differentiate into PSGL1 loCD4 + pre-Tfh-like cells via IL-6-Stat3-BCL6 pathway, and they interact with activated donor B cells to augment antibody production, and some of them remain PSGL1 hi. The majority of the injected alloreactive T cells differentiate into PSGL1 hi Th1/Tc1 cells to cause acute GVHD. Early after allo-HCT, donor-type CD4 +, and CD8 + T cells including autoreactive CD4 + T cells are activated by host APCs in the lymphoid tissues. In this review, we summarize new mechanistic findings from murine models of chronic GVHD, and we discuss the relevance of these insights to chronic GVHD pathogenesis in humans and their potential impact on clinical prevention and treatment.ī cell chronic graft-versus-host disease hematopoietic cell transplantation mouse models tissue resident memory T cell.Ĭopyright © 2021 Song, Kong, Martin and Zeng. Murine models of allo-HCT have made great contributions to our understanding pathogenesis of acute and chronic GVHD. ![]() Therefore, chronic GVHD remains the major cause of long-term morbidity and mortality after allo-HCT. Acute GVHD can often be effectively controlled by treatment with corticosteroids or other immunosuppressant for a period of weeks, but successful control of chronic GVHD requires much longer treatment. Antibodies produced by donor B cells contribute to the pathogenesis of chronic GVHD but not acute GVHD. Chronic GVHD has a more complex pathophysiology involving donor-derived T cells that recognize recipient-specific antigens, donor-specific antigens, and antigens shared by the recipient and donor. Acute GVHD represents an acute alloimmune inflammatory response initiated by donor T cells that recognize recipient alloantigens. ![]() GVHD can be divided into acute and chronic types. Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for hematologic malignancies, but its success is complicated by graft- versus-host disease (GVHD). ![]()
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