ABERRATIONS OF SUPPRESSOR T-CELLS IN HUMAN GRAFT VERSUS HOST DISEASE

To determine whether imbalances in immunoregulatory T-cell subsets exist in patients with graft-versus-host disease, we analyzed T cells in three patients with acute and in six patients with chronic graft-versus-host disease after bone-marrow transplantation. The normal human peripheral-blood T-cell compartment is composed of 80 per cent TH2– and 20 per cent TH2+ T cells, as defined by reactivity with subset-specific heteroantiserums. Human suppressor cells are TH2+, whereas helper cells are TH2–. Patients with acute and chronic graft-versus-host disease had abnormalities in these populations, and their T cells frequently bore la-like antigens. Patients with acute disease lacked TH2+ cells, and the reappearance of this subset preceded the cessation of disease activity. Chronic disease, in contrast, was more heterogeneous. Suppressor cells were lacking in two patients but increased in the other four. Two of these four patients had TH2+,Ia+ T cells, suggesting in vivo activation of suppressor cells. Studies showing that these TH2+,Ia+ cells actively suppressed the in vitro immune response support this hypothesis and suggest that the immunoregulatory cells may profoundly affect the overall immune response. (N Engl J Med 300:1061–1068, 1979) GRAFT-versus-host disease (GVHD) represents a major obstacle to the success of allogeneic bone-marrow transplantation for treatment of human disease.1 2 3 4 5 Acute and chronic forms of GVHD have been described.4 The acute form usually develops several weeks after transplantation and is characterized by fever, diarrhea, eosinophilia, a distinctive skin erythroderma and hepatic dysfunction. Acute GVHD is, however, generally self-limited. The chronic form, in contrast, occurs months after bone-marrow transplantation, with or without an antecedent, clinically recognizable acute phase of the disease. Chronic GVHD develops insidiously, is generally unrelenting and may be associated with sclerodermoid skin changes, hepatic failure and, secondarily, portal hypertension,. © 1979, Massachusetts Medical Society. All rights reserved.