Circulating activated suppressor T lymphocytes in aplastic anemia.
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.
Zoumbos
N C
NC
Gascón
P
P
Djeu
J Y
JY
Trost
S R
SR
Young
N S
NS
D000741:Anemia, Aplastic / Q000097:blood / Q000276:immunology*; D000954:Antigens, Surface / Q000032:analysis; D001853:Bone Marrow / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D006684:HLA-DR Antigens; D006410:Hematopoiesis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000145:classification; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000954:Antigens, Surface; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma