Circulating activated suppressor T lymphocytes in aplastic anemia

N Engl J Med. 1985 Jan 31;312(5):257-65. doi: 10.1056/NEJM198501313120501.

Abstract

We studied the mechanism of hematopoietic suppression in aplastic anemia by means of two-color flow microfluorometric analysis of lymphocyte subpopulations and correlated the results with the occurrence in vitro of hematopoietic suppression and interferon production. In 12 patients with aplastic anemia a striking increase was observed in a population of "activated" suppressor T lymphocytes, which were defined by binding of both anti-Leu-2 and anti-HLA-DR monoclonal antibodies (patients with aplastic anemia, 6.8 +/- 3.2 per cent [mean +/- S.D.]; normal subjects, 1.7 +/- 1.3; patients given multiple transfusions, 2.5 +/- 1.7). Tac antigen expression, another surface marker of lymphocyte activation, was increased on suppressor lymphocytes in all five patients examined (patients with aplastic anemia, 31 +/- 17 per cent; normal subjects, 0.7 +/- 0.24; patients given multiple transfusions, 2.3 +/- 1.2). When Tac+ and Tac- cells were separated in a cell sorter, only Tac+ cells produced interferon. When lymphocytes of patients with aplastic anemia were cocultured with normal bone marrow, only the Tac+ cell fraction showed hematopoietic suppressor activity. In one patient, in vitro elimination of suppressor lymphocytes by use of OKT8 antibody abolished spontaneous interferon production by bone-marrow cells. These results suggest that activated suppressor lymphocytes producing interferon have a role in the pathogenesis of bone-marrow failure, and indicate the usefulness of defined lymphokine and phenotypic markers in the study of aplastic anemia.

MeSH terms

  • Anemia, Aplastic / blood
  • Anemia, Aplastic / immunology*
  • Antigens, Surface / analysis
  • Bone Marrow / immunology
  • Cell Separation
  • Flow Cytometry
  • HLA-DR Antigens
  • Hematopoiesis
  • Histocompatibility Antigens Class II / analysis
  • Humans
  • Interferon-gamma / biosynthesis
  • Leukocyte Count
  • Lymphocyte Activation
  • Lymphocytes / classification
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7

Substances

  • Antigens, Surface
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Interferon-gamma