T cell antiviral effector function is not dependent on CXCL10 following murine coronavirus infection.
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-gamma 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.
Stiles
Linda N
LN
Department of Molecular Biology and Biochemistry and Center for Immunology, University of California-Irvine, Irvine, CA 92697, USA.
Hardison
Jenny L
JL
Schaumburg
Chris S
CS
Whitman
Lucia M
LM
Lane
Thomas E
TE
D000818:Animals; D001921:Brain / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D002630:Chemotactic Factors / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D018352:Coronavirus Infections / Q000276:immunology*; D007109:Immunity; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D002630:Chemotactic Factors