Generation of self HLA-DR-specific CD3+CD4-CD8+ cytotoxic T cells in chronic graft-versus-host disease.
To analyze the mechanism of chronic graft-versus-host disease (GVHD) characteristic of autoimmune disease, we used a cell-mediated lympholysis assay to study the autoreactivity of PBL from two patients after MHC-matched BMT. Our data indicate the induction of CD3+CD4-CD8+ autoreactive cytotoxic T lymphocytes (CTL) in the one patient with chronic GVHD and an important role for allo-non-MHC (minor histocompatibility) antigen-specific CD3+CD4+CD8- helper T cells in this induction. Experiments using HLA-DR gene-transfected mouse L cells as target cells and blocking assays with anti-HLA class I and class II antibodies provided evidence that autoreactive CTL recognized HLA-DR antigen on autologous cells. Analysis of antigen-specific T cell proliferative responses in these patients to examine the effect of self HLA-DR-specific CTL on the antigen presenting cell (APC)-T cell interaction suggested that donor bone marrow-derived self HLA-DR-specific CTL are responsible for the decreased antigen-presenting ability of the patient's APC. These results suggest a new interpretation of the induction mechanism of chronic GVHD and its associated immunosuppression after MHC-matched BMT based on diminished APC function.
Yamamoto
M
M
Department of Pediatrics, Hyogo College of Medicine, Nishinomiya, Japan.
Sugihara
K
K
Ohtsuki
F
F
Tsujino
Y
Y
Tanaka
A
A
Kamiya
T
T
Wada
H
H
Kanamaru
A
A
Hara
H
H
Yano
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000502:physiology; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002648:Child; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens