Role of in vivo activated T cells in the mechanisms of villous atrophy in humans: study of allograft rejection.
Four children aged 6 months to 9 years received fully HLA-mismatched ABO identical small intestinal allografts. In order to monitor the rejection process and to study epithelial changes induced by intestinal T cells activated by an allogeneic reaction, iterative biopsies were performed through the ileal enterostomy and processed for histology and immunohistochemistry. Episodes of acute histological reaction were observed in all 4 patients between day 10 and 160. It was preceded by appearance of pericryptic CD3+CD4+ or CD8+ T cells of recipient origin, increasing numbers of which expressed CD25. Simultaneously, early epithelial changes were noted: increased HLA-DR expression by enterocytes and decreased mitotic rate as shown by decreased numbers of KI67+ cells in crypts. During acute histological rejection, massive infiltration of mucosa by CD25+CD3+ T-cells and activated macrophages (KIM6+CD25+), was associated with crypt necrosis and then, destruction of surface epithelium. Successful treatment of graft rejection episodes with antilymphocytic serum (2), anti-CD3 monoclonal antibody (2), anti-CD25 monoclonal antibody (1) resulted in a rapid decrease of CD3+ cells, a more progressive decrease of CD25+ and KIM6+ macrophages, reappearance of KI67+ cells in crypts followed after a variable delay by recovery of villous architecture. Chronic histological rejection was observed in 1 patient after 7 months. It was characterized by total villous atrophy, fibrosis, endarteritis, infiltration of lamina propria and epithelium by CD3+CD8+ cells, a small number of which CD25+, strong HLA-DR expression by crypt and surface epithelium, increased numbers of KI67 enterocytes. Altogether these data suggested that activated T cells can induce two types of villous atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Cerf-Bensussan
N
N
INSERM U 132, Hôpital des Enfants-Malades, Paris, France.
Brousse
N
N
Jarry
A
A
Goulet
O
O
Revillon
Y
Y
Ricour
C
C
Guy-Grand
D
D
D001284:Atrophy; D002648:Child; D002675:Child, Preschool; D006084:Graft Rejection / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D007421:Intestine, Small / Q000637:transplantation*; D008213:Lymphocyte Activation / Q000276:immunology*; D008871:Microvilli / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*