Abnormalities of Immunoregulatory T Cells in Disorders of Immune Function

We studied a five-year-old girl with several autoimmune disorders and a 16-year-old boy with acquired agammaglobulinemia to determine whether aberrations of immunoregulatory T cells could explain some instances of immunodeficiency or autoimmunity. The normal peripheral blood T-cell population, as defined by specific heteroantiserums, is 20 per cent TH₂⁺ and 80 per cent TH₂^-. Human suppressor cells are TH₂⁺, whereas helper cells are TH₂^-. In addition, each subset expresses la antigens upon activation. Our patient with autoimmune disease had no demonstrable TH₂⁺ cells, and her lymphocytes could not be induced to suppress. Her circulating T cells were of an activated-helper phenotype, i.e., [m_i],Ia⁺. In contrast, in the boy with agammaglobulinemia, the T-cell population was predominantly of an activated-suppressor phenotype, i.e., [m_i],Ia⁺. This patient's T cells abrogated both his own and his histoidentical brother's B-cell secretion of immunoglobulins. We conclude that the characterization of T cells may provide insight into the causes of a number of abnormal immune states in man. (N Engl J Med 301:1018–1022, 1979) THE human T-cell population is composed of distinct subsets with unique functions.^{1 2 3 4 5 6} A delicate balance between effector and regulatory cells is required for immune homeostasis.^7,8 Aberrations in immunoregulatory T-cell subsets have been shown to exist in a number of human diseases.^{7 8 9} For example, patients with active juvenile rheumatoid arthritis lack a regulatory T-cell subset, termed JRA⁺, at a time when their serum contains autoantibodies reactive with this subset of cells.⁷ In the absence of this immunoregulatory influence, marked hyperglobulinemia develops in these patients. Recently, we have shown that patients with acute graft-versus-host disease after bone-marrow transplantation lack the TH.