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 clonal ity of the T cell population in patients who experience acute rejectio n (AR) following bone marrow transplantation (BMT) from a partially mi smatched related donor (PMRD). Phenotypic analysis was performed using flow cytometry, assignment of donor/host lineage by cytogenetics or H LA-specific flow cytometry, and analysis of the T cell receptor (TCR) by reverse-transcriptase polymerase chain reaction (RT-PCR). We have p reviously reported the initial appearance in the blood of AR patients of host CD8(+ bright)CD3(low) T cells that progressively express incre asing 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(+)H LA-DR(-)) usually associated with AR of grafts from matched sibling do nors. Analysis of the TCR V beta subsets from two patients revealed so rted host CD3(+)CD8(+) cells (purity 90-95%) from the first patient to express V beta 18 almost exclusively. In a second patient with late r ejection (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 ce lls are known to be associated with AR, cytotoxic and suppressor linea ges in AR from the same type of BMT and clonal distribution of T cells in AR have ndt been reported. Preliminary results suggest that V beta expression in AR of PMRD grafts is restricted and host T cell phenoty pe may vary. Further studies will investigate whether specific mismatc hes correlate with specific V beta usage and/or host T cell phenotype.