HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print April 18, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.1006641v1 82/1/44    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jain, P. Articles by Wigdahl, B. Search for Related Content PubMed PubMed Citation Articles by Jain, P. Articles by Wigdahl, B.

(Journal of Leukocyte Biology. 2007;82:44-56.)
© 2007 by Society for Leukocyte Biology

Modulation of dendritic cell maturation and function by the Tax protein of human T cell leukemia virus type 1

Pooja Jain^*, Jaya Ahuja^*, Zafar K. Khan^*, Saori Shimizu, Olimpia Meucci, Stephen R. Jennings^* and Brian Wigdahl^*,1

^* Departments of Microbiology and Immunology and
Pharmacology and Physiology, Institute for Molecular Medicine and Infectious Disease and Centers for Molecular Virology and Neuroimmunology and Cancer Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

¹ Correspondence: Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA. E-mail: bwigdahl{at}drexelmed.edu

ABSTRACT

Human T cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by the generation of an intense CTL cell response directed against the viral transactivator protein Tax. In addition, patients diagnosed with HAM/TSP exhibit rapid activation and maturation of dendritic cells (DC), likely contributing to the robust, Tax-specific CTL response. In this study, extracellular Tax has been shown to induce maturation and functional alterations in human monocyte-derived DC, critical observations being confirmed in freshly isolated myeloid DC. Tax was shown to promote the production of proinflammatory cytokines and chemokines involved in the DC activation process in a dose- and time-dependent manner. Furthermore, Tax induced the expression of DC activation (CD40, CD80, and CD86) and maturation (CD83) markers and enhanced the T cell proliferation capability of DC. Heat inactivation of Tax resulted in abrogation of these effects, indicating a requirement for the native structure of Tax, which was found to bind efficiently to the DC membrane and was internalized within a few hours, suggesting that extracellular Tax may possess an intracellular mechanism of action subsequent to entry. Finally, inhibitors of cellular signaling pathways, NF-B, protein kinase, tyrosine kinase, and phospholipase C, were shown to inhibit Tax-mediated DC activation. This is the first study reporting the immunomodulatory effects of extracellular Tax in the DC compartment. These results suggest that DC, once exposed to Tax by uptake from the extracellular environment, can undergo activation, providing constant antigen presentation and costimulation to T cells, leading to the intense T cell proliferation and inflammatory responses underlying HAM/TSP.

Key Words: HTLV-1 • HAM/TSP • Tax-specific CTL response

This article has been cited by other articles:

				P. Jain, K. Mostoller, K. E. Flaig, J. Ahuja, V. Lepoutre, T. Alefantis, Z. K. Khan, and B. Wigdahl Identification of Human T Cell Leukemia Virus Type 1 Tax Amino Acid Signals and Cellular Factors Involved in Secretion of the Viral Oncoprotein J. Biol. Chem., November 23, 2007; 282(47): 34581 - 34593. [Abstract] [Full Text] [PDF]