The immunopathology of upper gastrointestinal acute graft-versus-host disease. Lymphoid cells and endothelial adhesion molecules.
Acute graft-versus-host disease is a common complication of allogeneic bone marrow transplantation, but the mechanisms resulting in tissue injury are uncertain. In order to probe the effector phase of upper gastrointestinal acute GVHD, we performed immunopathologic studies of duodenal biopsies obtained from patients with or without GVHD. We evaluated the infiltrating mononuclear cells in both epithelium and lamina propria for expression of CD2, CD4, CD8, CD25, T alpha/beta and gamma/delta receptors, CD16, CD56, CD57 and also studied the distribution of cell adhesion molecules (ELAM-1, VCAM-1, ICAM-1, PECAM-1). In the epithelium, only a minimal T cell infiltrate was observed. In the lamina propria, GVHD tissue (vs. control) had an infiltrate of CD2+ (17.7 +/- 2.9% vs. 7.2 +/- 1.8%; P < 0.04), CD8+ (15.5 +/- 4.4% vs. 4.8 +/- 1.9%, P < 0.04) T lymphocytes. GVHD-positive and control tissues contained similar numbers of CD4+ T cells and natural killer cells (CD56+ or CD57+). ICAM-1 staining of endothelial cells was prominent in GVHD tissues (13.5 +/- 1.1 capillaries/field) and was significantly increased over non-GVHD specimens (7.5 +/- 1.8; P < 0.02). ELAM-1, VCAM-1, and PECAM-1 were similarly distributed in both biopsy groups. These data suggest that effectors of upper GI GVHD include CD2+, CD8+, T lymphocytes infiltrating the lamina propria. Inflammatory cell activation and resultant secretion of cytokines might directly damage the mucosa, but may also upregulate ICAM-1 on local endothelium leading to perpetuation of inflammation by recruitment of additional cytotoxic lymphocytes.
Roy
J
J
Department of Medicine, University of Minnesota, Minneapolis 55455.
Platt
J L
JL
Weisdorf
D J
DJ
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016827:CD8 Antigens / Q000032:analysis; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002648:Child; D016207:Cytokines / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D019040:E-Selectin; D004727:Endothelium / Q000737:chemistry / Q000166:cytology; D005260:Female; D005767:Gastrointestinal Diseases / Q000276:immunology / Q000473:pathology*; D006086:Graft vs Host Disease / Q000473:pathology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007694:Killer Cells, Natural / Q000166:cytology; D008214:Lymphocytes / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013194:Staining and Labeling
D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018799:Intercellular Adhesion Molecule-1