EPITHELIAL CLASS II ANTIGEN EXPRESSION IN CUTANEOUS GRAFT-VERSUS-HOST DISEASE

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Abstract
Induced class II histocompatibility antigens have been observed in the target tissues of rodents and humans with acute graft-versus-host disease (GVHD). Possibly this expression triggers the target tissue phase, through antigen presentation, lymphocyte recruitment, or additional antigenic stimulus. We have tested whether the induced expression is required for cutaneous GVHD in human marrow recipients. Ninety-two skin biopsies from 37 allogeneic marrow recipients at the Johns Hopkins Bone Marrow Transplant Unit were stained for HLA-DR, OKT6 (Langerhans cells), and for surface markers of lymphocyte and monocytes. Of 22 biopsies taken at the onset of GVHD, 12 did not have detectable HLA-DR antigen, and 10 had patchy-to-diffuse expression. The biopsies with HLA-DR−GVHD consisted primarily of epithelial infiltrates of cytotoxic/suppressor cells (CD8+), while those with HLA-DR+ GVHD had a mixed infiltrate with more helper/inducer/class-II-re-active cells (CD4+) in the epidermis and dermis and more monocytes in the dermis. Eight of 9 patients with HLA-DR−GVHD had follow-up biopsies that later expressed epithelial DR antigen, but the epidermal and dermal infiltrates showed no significant changes. Most of those receiving cyclosporine (CsA) prophylaxis (7/9) developed HLA-DR−GVHD, while those receiving cyclophosphamide were split between the two groups (8 of 13 were HLA-DR+). HLA-DR antigen expression was evident in some biopsies with no GVHD or minimal GVHD but did not appear to predict the development of GVHD or the type of GVHD. HLA-DR antigen expression was not evident in 2 of 3 initial biopsies of lichenoid-type chronic GVHD. Class II antigen induction is clearly not necessary for the target phase in most patients of this study.