Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 361K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Maloy, K. J. Articles by Hengartner, H. Search for Related Content PubMed PubMed Citation Articles by Maloy, K. J. Articles by Hengartner, H. Social Bookmarking                            What's this?

Original Article

Kevin J. Maloy^a, Christoph Burkhart^a, Tobias M. Junt^a, Bernhard Odermatt^a, Annette Oxenius^a, Luca Piali^b, Rolf M. Zinkernagel^a, and Hans Hengartner^a

^a Department of Pathology, Institute of Experimental Immunology, CH-8091 Zürich, Switzerland
^b Department of Research, University Children's Hospital, CH-4031 Basel, Switzerland
University of Oxford, Nuffield Department of Surgery, John Radcliffe Hospital, Level 6 Rm. 6602, Oxford OX3 9DU, UK.44-1865-76887644-1865-220410

kevin.maloy{at}nds.ox.ac.uk

To analyze the antiviral protective capacities of CD4⁺ T helper (Th) cell subsets, we used transgenic T cells expressing an I-A^b–restricted T cell receptor specific for an epitope of vesicular stomatitis virus glycoprotein (VSV-G). After polarization into Th1 or Th2 effectors and adoptive transfer into T cell–deficient recipients, protective capacities were assessed after infection with different types of viruses expressing the VSV-G. Both Th1 and Th2 CD4⁺ T cells could transfer protection against systemic VSV infection, by stimulating the production of neutralizing immunoglobulin G antibodies. However, only Th1 CD4⁺ T cells were able to mediate protection against infection with recombinant vaccinia virus expressing the VSV-G (Vacc-IND-G). Similarly, only Th1 CD4⁺ T cells were able to rapidly eradicate Vacc-IND-G from peripheral organs, to mediate delayed-type hypersensitivity responses against VSV-G and to protect against lethal intranasal infection with VSV. Protective capacity correlated with the ability of Th1 CD4⁺ T cells to rapidly migrate to peripheral inflammatory sites in vivo and to respond to inflammatory chemokines that were induced after virus infection of peripheral tissues. Therefore, the antiviral protective capacity of a given CD4⁺ T cell is governed by the effector cytokines it produces and by its migratory capability.

Key Words: Th1/Th2 cells • vesicular stomatitis virus • vaccinia • chemokines • migration

Abbreviations used in this paper: Bac-G, baculovirus-derived recombinant VSV-G; Bac-NP, baculovirus-derived recombinant VSV-NP; CCR, CC chemokine receptor; CNS, central nervous system; CXCR, CXC chemokine receptor; DTH, delayed-type hypersensitivity; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; LCMV, lymphocytic choriomeningitis virus; MCP, monocyte chemotactic protein; MDC, macrophage-derived chemokine; Mig, monokine induced by IFN-; MIP, macrophage inflammatory protein; RANTES, regulated upon activation, normal T cell expressed and secreted protein; RT, reverse transcription; SDF, stromal cell–derived factor; VSV, vesicular stomatitis virus; VSV-IND, VSV serotype Indiana; Vacc-IND-G, recombinant vaccinia virus expressing VSV-IND glycoprotein; VSV-NJ, VSV serotype New Jersey; UVⁱ-VSV, UV-inactivated VSV.

C. Burkhart and T.M. Junt contributed equally to this work.

C. Burkhart's present address is Department of Rheumatology and Clinical Immunology/Allergology, Inselsspital, CH-3010 Bern, Switzerland.

© 2000 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS