Abnormal expression of interleukin-2 receptor (Tac antigen) in adult T-cell leukemia.
Human T-cell leukemia/lymphoma virus type I(HTLV-I) infection appears to be closely associated with the leukemogenesis of adult T-cell leukemia (ATL), although its mechanism remains unclear. Since our previous report that leukemic cells from patients with ATL expressed Tac antigen (Ag) (interleukin-2 (IL-2) receptor) on their cell surface, we have been studying IL-2 receptors on ATL leukemic cells to see whether they are different from normal IL-2 receptors and whether they play a role in the neoplastic growth of ATL cells. Peripheral blood leukemic cells from 35 patients with ATL expressed IL-2 receptors which were detected by anti-Tac monoclonal antibody when examined immediately after the separation of cells or after culture for 24 or 48 hr. The number of anti-Tac binding sites ranged from 4,300 to 11,400 in fresh cells and from 6,100 to 96,000/cell in short term cultured leukemic cells, whereas phytohemagglutinin-P(PHA-P)-stimulated normal T cells exhibited 7,000 to 35,000 anti-Tac binding sites/cell. HTLV-I-infected cell lines such as MT-1 and HUT-102 expressed a markedly enhanced number of Tac Ag molecules. Leukemic cells from 15 ATL patients showed no or very poor proliferative response to various concentrations of IL-2, although they expressed Tac Ag. Radiolabeled IL-2 binding experiments revealed that ATL leukemic cells could bind IL-2 although the number of IL-2 binding sites was much less than that of anti-Tac binding sites. IL-2 receptors on ATL cells, unlike normal activated T cells, were not modulated (down-regulated) by anti-Tac antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
D000954:Antigens, Surface / Q000032:analysis* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007938:Leukemia / Q000378:metabolism*; D008970:Molecular Weight; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000032:analysis* / Q000378:metabolism; D015375:Receptors, Interleukin-2; D012192:Retroviridae Infections / Q000378:metabolism; D013601:T-Lymphocytes; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000954:Antigens, Surface; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7