title: Characterization of HTLV-I in vivo infected T cell clones. IL-2-independent growth of nontransformed T cells.
abstract: Mononuclear cells from subjects infected with human T lymphotrophic virus type I (HTLV-I) display a unique ability to proliferate in vitro in the absence of mitogens or exogenous growth factors. Subjects who have developed an HTLV-I-associated myelopathy (HAM) show an even higher degree of spontaneous proliferation concomitant with transcription of the HTLV-I provirus. The mechanism underlying HTLV-I-induced T cell activation was investigated by characterizing a series of HTLV-I-infected T cell clones generated from the blood of subjects with HAM. Approximately 15% of the T cell clones generated were HTLV-I infected as determined by polymerase chain reaction and Southern blotting. Infected T cell clones displayed altered growth kinetics as they continued to incorporate tritiated thymidine 7 to 14 days after stimulation, a time when noninfected T cell clones had returned to a resting state. This was not due to transformation as all the T cell clones required periodic restimulation with mitogens and feeder cells for continued growth. Although HTLV-I-infected T cell clones showed increased expression of the IL-2 receptor p55 chain, the spontaneous clonal proliferation was not inhibited by anti-IL-2 receptor mAb. Moreover, the spontaneous clonal proliferation was insensitive to cyclosporin A and FK 506 while being highly sensitive to rapamycin, which is known to inhibit IL-2-mediated signaling. Together these results demonstrate that IL-2 is not required for the HTLV-I-induced spontaneous clonal proliferation and further suggest that HTLV-I may induce signaling pathways replacing an IL-2 receptor signal proximal to the site of action of rapamycin.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115.
authors.forename: P
authors.initials: P
authors.lastname: Höllsberg
authors.forename: K W
authors.initials: KW
authors.lastname: Wucherpfennig
authors.forename: L J
authors.initials: LJ
authors.lastname: Ausubel
authors.forename: V
authors.initials: V
authors.lastname: Calvo
authors.forename: B E
authors.initials: BE
authors.lastname: Bierer
authors.forename: D A
authors.initials: DA
authors.lastname: Hafler
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D001483:Base Sequence; D017252:CD3 Complex; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology; D015490:HTLV-I Infections / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011090:Polyenes / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000502:physiology; D020123:Sirolimus; D013601:T-Lymphocytes / Q000382:microbiology*; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011090:Polyenes; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus