Measurement of recipient-specific alloreactivity: is GVHD predictable?
Acute graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. There is no practical test before transplantation that gives sufficient information to predict the degree of allogeneic reactivity between HLA-identical siblings. We determined the frequency with which host-specific interleukin-2 (IL-2) -secreting donor T lymphocyte precursors (Tl-p) occurred in 16 pairs of HLA-identical siblings before they underwent marrow grafting. The results were correlated with the development of acute GVHD after BMT. We further analyzed the responding host (and donor) -specific Tl-p with respect to the cell surface phenotype, the influence of previous in vivo priming, and the MHC class restriction of minor histocompatibility (mH) antigen recognition. To investigate whether host-reactive Tl-p are involved in the induction of acute GVHD, we also examined the frequency of host-specific Tl-p at various time intervals after BMT in 14 patients with and without acute GVHD. High frequencies of host-specific Tl-p were detectable before BMT in 8 donors whose siblings later had severe (grade II or III) acute GVHD. Among the donors to 8 patients with mild (grade 0 or I) acute GVHD, low frequencies were found. Various T-cell subsets contributed to the responding Tl-p. The presence of host-specific Tl-p after BMT was significantly correlated with the development of serious (grade II or III) acute GVHD. We conclude that host-specific IL-2-secreting T cells are critically involved in the induction and maintenance of acute GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
Theobald
M
M
Department of Immunology, Scripps Research Institute, La Jolla, CA.
Bunjes
D
D
Nierle
T
T
Arnold
R
R
Heimpel
H
H
D000208:Acute Disease; D000918:Antibody Specificity; D001853:Bone Marrow / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D015994:Incidence; D007376:Interleukin-2 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014019:Tissue Donors; D014184:Transplantation, Homologous
D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D017493:Leukocyte Common Antigens