Fig. 5.34 Chronic rejection. (A) Graft arteriosclerosis caused by T-cell cytokines and antibody deposition. (B) Graft arteriosclerosis in a cardiac transplant. (C) Transplant glomerulopathy, the characteristic manifestation of chronic antibody-mediated rejection in the kidney. The glomerulus shows inflammatory cells within the capillary loops (glomerulitis), accumulation of mesangial matrix, and duplication of the capillary basement membrane. (D) Interstitial fibrosis and tubular atrophy, resulting from arteriosclerosis of arteries and arterioles in a chronically rejecting kidney allograft. In this trichrome stain, the blue area (asterisk) shows fibrosis, contrasted with the normal kidney (top right). An artery showing prominent arteriosclerosis is shown (bottom right). (B, Courtesy of Dr. Richard Mitchell, Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts. C and D, Courtesy of Dr. Zoltan Laszik, Department of Pathology, University of California, San Francisco, California.) donor graft perceive the host’s tissue as foreign and react There are two forms of GVHD. against it. This results in the activation of donor CD4+ and • Acute GVHD (occurring days to weeks after transplanCD8+ T cells, ultimately causing inflammation and killing tation) causes epithelial cell necrosis in three principal recipient cells. To try to minimize GVHD, HSC transplants target organs: liver, skin, and gut. Destruction of small are done between donor and recipient that are carefully bile ducts gives rise to jaundice, and mucosal ulcerHLA-matched using precise DNA sequencing–based  ation of the gut results in bloody diarrhea. Cutanemethods. ous involvement (
Fig. 5.35 ) manifests as a rash, which
Fig. 5.35 Acute graft-versus-host disease (GVHD) involving the skin. (A) Patchy epithelial cell death and dermal infiltrates of mononuclear cells (lymphocytes and macrophages). (B) Focally dead epithelial cells (arrows).
characteristically appears first on the neck, ears, and palms of the hands and soles of the feet and then becomes generalized.
• Chronic GVHD may follow the acute syndrome or may occur insidiously. Patients develop skin lesions resembling those of systemic sclerosis (discussed earlier) and manifestations mimicking other autoimmune disorders.
Because GVHD is mediated by T lymphocytes contained in the transplanted donor cells, depletion of donor T cells before transplantation virtually eliminates the disease. This approach, however, has proven to be a mixed blessing: GVHD is ameliorated, but the recurrence of tumor in leukemic patients as well as the incidence of graft failures and EBV-related B-cell lymphoma increase. It seems that the multifaceted T cells not only mediate GVHD but also are required for engraftment of the transplanted HSCs, suppression of EBV-infected B-cell clones, and control of leukemia cells.