IL-2- and IL-2-R- independent proliferation of T-cell lines from adult T-cell leukemia/lymphoma patients.
Human T-cell leukemia/lymphoma virus I (HTLV-I) is known to be associated with adult T-cell leukemia/lymphoma (ATL) as an etiological agent. The mechanism of leukemogenesis by HTLV, however, is still obscure. Two hypotheses have been proposed concerning abnormalities in IL-2 production and its receptor (Tac antigen) expression based on the experimental observations of IL-2-dependent ATL cell lines. In this study, we examine these hypotheses by using 3 leukemic T-cell lines from 3 Japanese patients with ATL. These cell lines were cultivated and established without addition of IL-2 to the culture medium. Cell-surface phenotype analysis by immunofluorescence with monoclonal antibodies (MAbs) and IL-2 binding assays revealed that one of the ATL cell lines, HPB-ATL-2, expresses only a minimal amount of IL-2 receptor (IL-2-R) on the cell surface and binds less radiolabelled human recombinant IL-2 than the other highly Tac-positive cell lines. Expression of Tac antigen in all ATL cell lines was not affected by IL-2, anti-Tac MAb or the tumor-promoter phorbol ester in the culture medium. The culture supernatant from these cell lines showed no IL-2 activity toward Con-A-stimulated human peripheral blood lymphocytes, and their growth was not affected by additional IL-2 in cultures. IL-2-independent growth and constitutive expression of its receptors on the cell surface were evident in our ATL cell lines. However, dense expression of IL-2 receptors was not essential for stimulation of leukemic proliferation of T cells by HTLV-I. Trans-activation of the PX40 gene product of HTLV-I for activation of IL-2-R gene might not be coincidentally associated with stimulation for cell proliferation.
Katoh
T
T
Harada
T
T
Morikawa
S
S
Wakutani
T
T
D000328:Adult; D000954:Antigens, Surface / Q000032:analysis; D000956:Antigens, Viral / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006800:Deltaretrovirus Infections / Q000209:etiology*; D066246:ErbB Receptors; D005814:Genes, Viral; D015488:HIV Antigens; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis; D008297:Male; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis* / Q000235:genetics; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000954:Antigens, Surface; D000956:Antigens, Viral; D015488:HIV Antigens; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate