Sequential immunohistologic analysis of the skin following allogeneic bone marrow transplantation

Abstract

Graft-vs-host disease is generally viewed as an immunologically mediated disease. In search of additional tools for early diagnosis and an elucidation of the pathogenic mechanisms we investigated the expression kinetics of hemopoietic differentiation and class II alloantigens on both resident and passenger skin cells after bone marrow transplantation. HLA-DR antigens, which are found normally on the dendritic epidermal Langerhans cells only, are synthesized and expressed by keratinocytes within lesions of acute and chronic cutaneous graft-vs-host disease. Within non-lesional skin, however, during the course of cutaneous graft-vs-host eruptions, no clear cut expression of keratinocyte-bound HLA-DR antigens can be identified, suggesting that this phenomenon is locally restricted rather than generalized. Furthermore, our data indicate that within lesions clinically suggestive of cutaneous graft-vs-host disease but lacking diagnostic histopathologic criteria, KC-bound HLA-DR antigens can be readily identified. The second class II alloantigens investigated within the epidermis, the HLA-DQ antigens, were seen on Langerhans cells only and were not or only rarely detectable on keratinocytes. Several subtypes of CD3+ T lymphocytes were present in the epidermis of acute graft-versus-host lesions: one portion of CD3+ T lymphocytes also displayed the CD8 antigen; one portion, mainly localized within the basal layer, displayed the CD8 and/or the CD4 antigen; and one portion did not allow identification of CD8, CD4, or Leu7 antigens. In chronic cutaneous graft-versus-host lesions CD3+/CD8+ T lymphocytes predominated. CD1+ epidermal Langerhans cells were reduced in number and appeared rounded with blunt dendrites both in acute and chronic cutaneous graft-vs-host disease, but also, though to a lesser extent, within normal appearing skin from bone marrow transplanted patients without cutaneous graft-vs-host disease.