Ls. Lamb et al., CHARACTERIZATION OF ACUTE BONE-MARROW GRAFT-REJECTION IN T-CELL-DEPLETED, PARTIALLY MISMATCHED RELATED DONOR BONE-MARROW TRANSPLANTATION, Experimental hematology, 23(14), 1995, pp. 1595-1600
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.