Characterization of skin-infiltrating cells during acute graft-versus-host disease following bone marrow transplantation using unrelated marrow donors

Afzal Nikaein, Twyala Poole, Randi Fishbeck, Guido Ordonez, Lori Dombrausky, Marvin J. Stone, Robert H. Collins, Joseph W. Fay

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

To characterize skin-infiltrating T lymphocytes during acute GVHD, skin biopsies were obtained from two patients who received unrelated marrow 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 α/β TCR. HLA-DP oligonucleotide genotyping of the clones revealed the presence of lymphoid chimerism. PLT assay showed the lack of HLA specificity, including mismatched HLA-DP. However, mAb to HLA antigens blocked proliferation of the majority of the clones, indicating that the clones 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 proliferation in the presence of CMV antigens and a few revealed cytolytic activity. The above study suggests that (a) CD4+ helper T cells may be primarily responsible for immunopathogenesis of skin manifestations during acute GVHD, (b) there is a mixed lymphoid chimerism in skin during acute GVHD, (c) HLA-DP may not be a factor contributing to the development of acute GVHD, (d) the peptide of the HLA groove or superantigen associated with HLA molecules may be the stimulatory antigen, and (e) CMV antigens appear to stimulate some of the skin-infiltrating T lymphocytes.

Original languageEnglish (US)
Pages (from-to)68-76
Number of pages9
JournalHuman Immunology
Volume40
Issue number1
DOIs
StatePublished - May 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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