Characterization of HTLV-I in vivo infected T cell clones. IL-2-independent growth of nontransformed T cells

J Immunol. 1992 May 15;148(10):3256-63.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antigens, Differentiation, T-Lymphocyte / physiology
  • Base Sequence
  • CD3 Complex
  • Clone Cells
  • Cyclosporine / pharmacology
  • HTLV-I Infections / immunology*
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / physiology*
  • Lymphocyte Activation*
  • Molecular Sequence Data
  • Polyenes / pharmacology
  • RNA, Messenger / analysis
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Interleukin-2 / analysis
  • Receptors, Interleukin-2 / physiology
  • Sirolimus
  • T-Lymphocytes / microbiology*
  • Tacrolimus / pharmacology

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Interleukin-2
  • Polyenes
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Cyclosporine
  • Sirolimus
  • Tacrolimus