Increased cell turnover, but no signs of increased T-cell infiltration or inflammatory cytokines in the duodenum of pediatric patients after allogeneic stem cell transplantation.
Intestinal immunopathology was studied after allogeneic stem cell transplantation (SCT) in a common clinical setup in 20 children with malignant (n=17) or nonmalignant diseases (n=3) receiving grafts from siblings (7) and unrelated donors (13). In all, 19 had total body irradiation. Duodenal biopsies at 6 and 12 weeks post transplant were evaluated by histology, immunohistochemistry, and ISEL for the detection of T-lymphocytes, inflammatory cytokines, proliferation, and apoptosis. The controls were 12 healthy children and three patients with proven intestinal graft-versus-host disease. An increased rate of apoptosis and proliferation with upregulated expression of HLA-DR antigen was detected up to 3 months post transplant in the SCT patients, even in those with a histologically normal small intestine. A low level of IFNgamma and TNFalpha was observed in the lamina propria. The initial low density of gammadelta-positive T cells had recovered to normal by the time of the second endoscopy at 12 weeks post transplant. We conclude that inflammatory activity and T cell infiltration detected by immunohistochemistry may not belong to the 'normal' recovery of the small intestine after SCT. Increased cell turnover in the intestinal crypts continues until 3 months after SCT, suggesting either an unexpectedly long-lasting effect of transplant-related toxicity or, preferably, an ongoing subclinical alloreactive process, also present in the patients without intestinal symptoms.
Taskinen
M
M
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. mervi.taskinen@hus.fi
Westerholm-Ormio
M
M
Karikoski
R
R
Lindahl
H
H
Veres
G
G
Savilahti
E
E
Saarinen-Pihkala
U M
UM
D000293:Adolescent; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism*; D004386:Duodenum / Q000276:immunology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007249:Inflammation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology* / Q000473:pathology; D014916:Whole-Body Irradiation
D016207:Cytokines; D006684:HLA-DR Antigens