Characterization of acute bone marrow graft rejection in T cell-depleted, partially mismatched related donor bone marrow transplantation.
The purpose of this study was to characterize the phenotype and clonality of the T cell population in patients who experience acute rejection (AR) following bone marrow transplantation (BMT) from a partially mismatched related donor (PMRD). Phenotypic analysis was performed using flow cytometry, assignment of donor/host lineage by cytogenetics or HLA-specific flow cytometry, and analysis of the T cell receptor (TCR) by reverse-transcriptase polymerase chain reaction (RT-PCR). We have previously reported the initial appearance in the blood of AR patients of host CD8+brightCD3low T cells that progressively express increasing amounts of CD3+ cells. We now report that this cell population can differentiate into either a cytotoxic T cell phenotype (CD3+CD8+HLA-DR+CD57-) usually associated with AR of grafts from matched unrelated donors or a suppressor T cell phenotype (CD3+CD8+CD57+HLA-DR-) usually associated with AR of grafts from matched sibling donors. Analysis of the TCR V beta subsets from two patients revealed sorted host CD3+CD8+ cells (purity 90-95%) from the first patient to express V beta 18 almost exclusively. In a second patient with late rejection (55 days post-BMT), the CD3+CD8+ cells were predominantly restricted to V beta 1, 5.1, 7, 9, and 18. Although CD3+CD8+ T cells are known to be associated with AR, cytotoxic and suppressor lineages in AR from the same type of BMT and clonal distribution of T cells in AR have not been reported. Preliminary results suggest that V beta expression in AR of PMRD grafts is restricted and host T cell phenotype may vary. Further studies will investigate whether specific mismatches correlate with specific V beta usage and/or host T cell phenotype.
Center for Cancer Treatment and Research, Richland Memorial Hospital, Columbia, SC 29203, USA.
L S
LS
Lamb
F
F
Szafer
P J
PJ
Henslee-Downey
M
M
Walker
S
S
King
K
K
Godder
A R
AR
Pati
R
R
Best
L
L
Steinman
S S
SS
Geier
D001483:Base Sequence; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000032:analysis; D018959:CD57 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005434:Flow Cytometry; D006084:Graft Rejection; D006684:HLA-DR Antigens / Q000032:analysis; D006648:Histocompatibility; D006801:Humans; D016130:Immunophenotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014019:Tissue Donors
D017252:CD3 Complex; D018959:CD57 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell