| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Molecular Biology and Biochemistry and Center for Immunology, University of California, Irvine, CA 92697
The chemokine CXCL10 is expressed within the CNS in response to intracerebral infection with mouse hepatitis virus (MHV). Blocking CXCL10 signaling results in increased mortality accompanied by reduced T cell infiltration and increased viral titers within the brain suggesting that CXCL10 functions in host defense by attracting T cells into the CNS. The present study was undertaken to extend our understanding of the functional role of CXCL10 in response to MHV infection given that CXCL10 signaling has been implicated in coordinating both effector T cell generation and trafficking. We show that MHV infection of CXCL10+/+ or CXCL10–/– mice results in comparable levels of T cell activation and similar numbers of virus-specific CD4+ and CD8+ T cells. Subsequent analysis revealed no differences in T cell proliferation, IFN-
secretion by virus-specific T cells, or CD8+ T cell cytolytic activity. Analysis of chemokine receptor expression on CD4+ and CD8+ T cells obtained from MHV-immunized CXCL10+/+ and CXCL10–/– mice revealed comparable levels of CXCR3 and CCR5, which are capable of responding to ligands CXCL10 and CCL5, respectively. Adoptive transfer of splenocytes acquired from MHV-immunized CXCL10–/– mice into MHV-infected RAG1–/– mice resulted in T cell infiltration into the CNS, reduced viral burden, and demyelination comparable to RAG1–/– recipients of immune CXCL10+/+ splenocytes. Collectively, these data imply that CXCL10 functions primarily as a T cell chemoattractant and does not significantly influence T cell effector response following MHV infection.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants NS41249 and NS18146 (to T.E.L.).
2 L.N.S. and J.L.H. contributed equally to this work.
3 Address correspondence and reprint requests to Dr, Thomas E. Lane, Department of Molecular Biology and Biochemistry, 3205 McGaugh Hall, University of California, Irvine, Irvine, CA 92697-3900. E-mail address: tlane{at}uci.edu
4 Abbreviations used in this paper: i.c., intracerebral; MHV, mouse hepatitis virus; p.i., postinfection; M, transmembrane protein; S, surface glycoprotein.
This article has been cited by other articles:
|
|
 |
|
  K. B. Walsh, M. B. Lodoen, R. A. Edwards, L. L. Lanier, and T. E. Lane Evidence for Differential Roles for NKG2D Receptor Signaling in Innate Host Defense against Coronavirus-Induced Neurological and Liver Disease J. Virol., March 15, 2008; 82(6): 3021 - 3030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zhang, Y. K. Chan, B. Lu, M. S. Diamond, and R. S. Klein CXCR3 Mediates Region-Specific Antiviral T Cell Trafficking within the Central Nervous System during West Nile Virus Encephalitis J. Immunol., February 15, 2008; 180(4): 2641 - 2649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Walsh, R. A. Edwards, K. M. Romero, M. V. Kotlajich, S. A. Stohlman, and T. E. Lane Expression of CXC Chemokine Ligand 10 from the Mouse Hepatitis Virus Genome Results in Protection from Viral-Induced Neurological and Liver Disease J. Immunol., July 15, 2007; 179(2): 1155 - 1165. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
