Lymphocytes with a CD4⁺ CD8^- CD3^- phenotype are effectors of experimental cutaneous graft-versus-host disease

Graft-versus-host disease (GVHD) is known to cause profound dysregulation of the immune system, although its effector mechanisms are poorly understood. We now describe an effector lymphocyte of unusual phenotype in the skin of mice with GVHD. This cell is of donor origin and expresses several T-cell surface proteins including Thy-1, CD2, and CD4 but does not express CDS, CD3, NK1.1, or macrophage antigens. Mononuclear cells of this phenotype are the predominant lymphocyte in the epidermis of mice with GVHD 3 weeks after transplant but are not detected in transplanted mice without GVHD. Isolation and transfer of these lymphocytes into secondary recipients causes epidermal damage characteristic of GVHD. These data demonstrate that CD4⁺ CD8^- CD3^- lymphocytes are an important effector population that can be amplified outside the thymus and that can mediate target organ damage of GVHD.