The Journal of Immunology, Vol 148, Issue 10 3256-3263, Copyright © 1992 by American Association of Immunologists

ARTICLES

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

P Hollsberg, KW Wucherpfennig, LJ Ausubel, V Calvo, BE Bierer and DA Hafler
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115.

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.

This article has been cited by other articles:

				C. Baecher-Allan, E. Wolf, and D. A. Hafler MHC class II expression identifies functionally distinct human regulatory T cells. J. Immunol., April 15, 2006; 176(8): 4622 - 4631. [Abstract] [Full Text] [PDF]

				B. Oster and P. Hollsberg Viral Gene Expression Patterns in Human Herpesvirus 6B-Infected T Cells J. Virol., June 27, 2002; 76(15): 7578 - 7586. [Abstract] [Full Text] [PDF]

				N. J. Rose and A. M. L. Lever The rapamycin sensitivity of human T-cell leukaemia virus type I-induced T-cell proliferation is mediated independently of the polypyrimidine motifs in the 5' long terminal repeat J. Gen. Virol., February 1, 2001; 82(2): 435 - 439. [Abstract] [Full Text]

				C. R M Bangham HTLV-1 infections J. Clin. Pathol., August 1, 2000; 53(8): 581 - 586. [Abstract] [Full Text] [PDF]

				P. Riou, F. Bex, and L. Gazzolo The Human T Cell Leukemia/Lymphotropic Virus Type 1 Tax Protein Represses MyoD-dependent Transcription by Inhibiting MyoD-binding to the KIX Domain of p300. A POTENTIAL MECHANISM FOR Tax-MEDIATED REPRESSION OF THE TRANSCRIPTIONAL ACTIVITY OF BASIC HELIX-LOOP-HELIX FACTORS J. Biol. Chem., March 31, 2000; 275(14): 10551 - 10560. [Abstract] [Full Text] [PDF]

				N. J. Rose, J. H. Richardson, U. Desselberger, and A. M. L. Lever Virus inactivation in a proportion of human T-cell leukaemia virus type I-infected T-cell clones arises through naturally occurring mutations J. Gen. Virol., January 1, 2000; 81(1): 97 - 104. [Abstract] [Full Text]

				P. Hollsberg Mechanisms of T-Cell Activation by Human T-Cell Lymphotropic Virus Type I Microbiol. Mol. Biol. Rev., June 1, 1999; 63(2): 308 - 333. [Abstract] [Full Text] [PDF]

				I. Lemasson, S. Thebault, C. Sardet, C. Devaux, and J.-M. Mesnard Activation of E2F-mediated Transcription by Human T-cell Leukemia Virus Type I Tax Protein in a p16INK4A-negative T-cell Line J. Biol. Chem., September 4, 1998; 273(36): 23598 - 23604. [Abstract] [Full Text] [PDF]

				M. S. Kraft, G. Henning, H. Fickenscher, D. Lengenfelder, J. Tschopp, B. Fleckenstein, and E. Meinl Herpesvirus Saimiri Transforms Human T-Cell Clones to Stable Growth without Inducing Resistance to Apoptosis J. Virol., April 1, 1998; 72(4): 3138 - 3145. [Abstract] [Full Text] [PDF]

				N. Azimi, K. Brown, R. N. Bamford, Y. Tagaya, U. Siebenlist, and T. A. Waldmann Human T cell lymphotropic virus type I Tax protein trans-activates interleukin 15 gene transcription through an NF-kappa B site PNAS, March 3, 1998; 95(5): 2452 - 2457. [Abstract] [Full Text] [PDF]

				J.H. Richardson, P. Hollsberg, A. Windhagen, L.A. Child, D.A. Hafler, and A.M.L. Lever Variable Immortalizing Potential and Frequent Virus Latency in Blood-Derived T-Cell Clones Infected With Human T-Cell Leukemia Virus Type I Blood, May 1, 1997; 89(9): 3303 - 3314. [Abstract] [Full Text] [PDF]

				T. Migone, J. Lin, A Cereseto, J. Mulloy, J. O'Shea, G Franchini, and W. Leonard Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I Science, July 7, 1995; 269(5220): 79 - 81. [Abstract] [PDF]

				P. Hollsberg and D. A. Hafler Pathogenesis of Diseases Induced by Human Lymphotropic Virus Type I Infection N. Engl. J. Med., April 22, 1993; 328(16): 1173 - 1182. [Full Text]