Immunohistochemical identification of perforin-positive cytotoxic lymphocytes in graft-versus-host disease.

To study the role of functionally active cytotoxic lymphocytes in human graft-versus-host disease (GVHD), perforin expression in infiltrating mononuclear cells was immunohistochemically investigated in skin biopsy specimens. Perforin is a component of intracytoplasmic granules of cytotoxic lymphocytes and serves as a specific marker of functionally active cytotoxic lymphocytes. The study included two cases of transfusion-associated GVHD, seven cases of acute GVHD and five cases of lichenoid chronic GVHD after allogeneic bone marrow transplantation. All specimens obtained from transfusion-associated GVHD and one case of acute GVHD with extracutaneous involvement contained a significant number of perforin-positive lymphocytes. In contrast, perforin-positive lymphocytes were few or absent in the other six cases of acute GVHD and in all five cases of lichenoid chronic GVHD after bone marrow transplantation. These findings suggest that perforin-mediated cytolysis by cytotoxic lymphocytes may be a major effector mechanism in transfusion-associated GVHD and at least in some cases of acute GVHD after bone marrow transplantation.