CHARACTERIZATION OF SKIN-INFILTRATING CELLS DURING ACUTE GRAFT-VERSUS-HOST DISEASE FOLLOWING BONE-MARROW TRANSPLANTATION USING UNRELATED MARROW DONORS

To characterize skin-infiltrating T lymphocytes during acute GVHD, ski n biopsies were obtained from two patients who received unrelated marr ow matched for HLA-A, -B, -DR, and -DQ but mismatched for -DP. A total of 120 T-cell clones were generated. Phenotype analysis of the clones showed that the majority of cells were CD4(+) and expressed alpha/bet a TCR. HLA-DP oligonucleotide genotyping of the clones revealed the pr esence of lymphoid chimerism. PLT assay showed the lack of HLA specifi city, including mismatched HLA-DP. However, mAb to HLA antigens blocke d proliferation of the majority of the clones, indicating that the clo nes recognized HLA-associated molecules. Interestingly, proliferation of two CD4(+) T-cell clones was inhibited by class I mAb. A few of the clones revealed augmented prolifer ation in the presence of CMV antig ens and a few revealed cytoletic activity. The above study suggests th at (a) CD4(+) helper T cells may be primarily responsible for immunopa thogenesis of skin manifestations during acute GVHD, (b) there is a mi xed lymphoid chimerism in skin during acute GVHD, (c) HLA-DP may not b e a factor contributing to the development of acute GVHD, (d) the pept ide of the HLA groove or superantigen associated with HLA molecules ma y be the stimulatory antigen, and (e) CMV antigens appear to stimulate some of the skin-infiltrating T lymphocytes.