Quantitative assessment of posttransplant host-specific interleukin-2-secreting T-helper cell precursors in patients with and without acute graft-versus-host disease after allogeneic HLA-identical sibling bone marrow transplantation.
Recent studies in mice and humans have emphasized an important contribution of host-reactive minor histocompatibility antigen (mH)-specific lymphokine-secreting donor T-helper cells (Th) for the induction of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). By using limiting dilution (LD) and clonal specificity analyses, we investigated in 14 patients with and without acute GVHD after non-T-depleted HLA-identical sibling BMT whether posttransplant host-reactive mH-specific interleukin-2 (IL-2)-secreting Th are involved in the development of clinically significant acute GVHD and the establishment of tolerance. At different time intervals posttransplant (I, days 0 through 45; II, days 45 through 90; III, days 90 through 180), host-specific IL-2-secreting Th-precursors (Th-p) were quantitatively assessed in six patients during clinically apparent grade II-III acute GVHD. Frequencies of responding Th-p ranged from 1/13,000 to 1 4,000. The presence of host-specific Th-p was significantly correlated with the development of grade II-III acute GVHD (P = .0003 by Fisher's exact test). The detectability of host-specific Th-p preceded the clinical onset of grade II-III acute GVHD. Host-specific Th-p were no longer detectable after the clinical resolution of grade II-III acute GVHD. No subsequent chronic GVHD was observed in these patients. However, prolonged occurrence of host-specific Th-p was accompanied by clinically persisting acute GVHD and the onset of secondary chronic GVHD. In patients with no acute GVHD (grade 0) (n = 7) and grade I (n = 1) acute GVHD, host-specific Th-p were not detectable at all. We conclude that host-reactive Th are critically involved in the development and maintenance of acute GVHD and may contribute to the establishment of tolerance after genotypically HLA-identical sibling BMT.
Nierle
T
T
Department of Internal Medicine III, University of Ulm, Germany.
Bunjes
D
D
Arnold
R
R
Heimpel
H
H
Theobald
M
M
D000208:Acute Disease; D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology / Q000601:surgery; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007376:Interleukin-2 / Q000096:biosynthesis*; D007938:Leukemia / Q000276:immunology / Q000601:surgery; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000601:surgery; D009679:Nuclear Family; D013234:Stem Cells / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D007166:Immunosuppressive Agents; D007376:Interleukin-2