Peripheral blood stem cell allograft rejection mediated by CD4(+) T lymphocytes recognizing a single mismatch at HLA-DP beta 1*0901.
Little is known about the molecular characteristics of alloantigens recognized by alloreactive T cells mediating hematologic stem cell graft rejection. In particular, it has never been shown that such alloantigens can be encoded by HLA-DP beta alleles. Indeed, matching for HLA-DP antigens is generally not considered to be of functional importance for the outcome of allogeneic bone marrow or peripheral blood stem cell transplantation. In this study, a case of peripheral blood stem cell allograft rejection was investigated in which the patient and donor differed for a single mismatch at HLA-DP in the rejection direction. Patient-derived T lymphocytes circulating at the time of rejection showed direct ex vivo cytotoxic activity against donor-derived B-lymphoblastoid cells as well as other HLA-DP beta 1*0901--expressing targets. The presence of HLA-DP beta 1*0901--specific effectors in vivo was further confirmed by in vitro stimulation experiments. CD4(+) T-cell lines and clones with specific cytotoxic activity against HLA-DP beta 1*0901--expressing targets including donor B-lymphoblastoid cells were generated both by nonspecific and by donor-specific in vitro stimulation. Taken together, these data demonstrate that HLA-DP can be the target antigen of cytotoxic CD4(+) T lymphocytes involved in peripheral blood stem cell allograft rejection. (Blood. 2001;98:1122-1126)
Fleischhauer
K
K
HLA Tissue Typing Laboratory, Istituto Scientifico H.S. Raffaele, Milan, Italy. katharina.fleischauer@hsr.it
Zino
E
E
Mazzi
B
B
Sironi
E
E
Servida
P
P
Zappone
E
E
Benazzi
E
E
Bordignon
C
C
D000328:Adult; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005220:Fathers; D005260:Female; D006084:Graft Rejection / Q000139:chemically induced / Q000276:immunology*; D006682:HLA-DP Antigens / Q000276:immunology / Q000494:pharmacology*; D059868:HLA-DP beta-Chains; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006648:Histocompatibility / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous / Q000009:adverse effects*
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C434668:HLA-DPB1*09:01 antigen