Abnormal in vitro proliferation and differentiation of T colony-forming cells in patients with lymphadenopathy syndrome.
Patients with acquired immunodeficiency syndrome (AIDS) present impaired colony growth and in vitro differentiation capacity of peripheral blood and bone marrow T colony-forming cells (T-CFC). We show that peripheral blood, bone marrow, and lymph node T-CFC from patients with persistent lymphadenopathy syndrome (LAS), a syndrome that can precede AIDS, displayed similar abnormalities. Indeed, peripheral blood T-CFC generated a low number of colonies in seven out of 12 patients, and almost no colonies were obtained from bone marrow cells of all patients. The simultaneous study of T-CFC from peripheral blood and lymph node mononuclear cells seems to provide a reliable indicator for the risk of developing AIDS. The six patients who developed AIDS displayed extremely low numbers of peripheral blood T-CFC (13 +/- 17 colonies per 5 X 10(4) cells), and in two of them, no colonies could be obtained from lymph node T-CFC. The remaining patients who had not developed AIDS displayed a higher number of peripheral blood T-CFC (141 +/- 113 per 5 X 10(4) cells) and lymph node T-CFC, which, in addition, preserved their clonogenic capacity. In some patients, peripheral blood and lymph node, but not bone marrow, T-CFC were capable of generating colonies in the absence of added growth factors or mitogens, whereas in others, colony formation was obtained with purified interleukin 2 (IL 2) alone. Both spontaneous and IL 2-induced colony formation was abrogated by a monoclonal antibody against the IL 2 receptor. Taken together, these findings suggest that at least some T-CFC expressed IL 2 receptors. Colonies generated either in the presence or in the absence of added growth factors were composed of T4+, T6+, and T8+ cells, indicating impaired in vitro T-CFC differentiation. These findings indicate that a dramatic quantitative and qualitative impairment of the proliferation and differentiation of peripheral blood and lymph node T-CFC precedes the clinical evolution from LAS to AIDS.
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D003114:Colony-Forming Units Assay; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000473:pathology*; D008297:Male; D010641:Phenotype; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000473:pathology*
D006133:Growth Substances