T Cell Antiviral Effector Function Is Not Dependent on CXCL10 Following Murine Coronavirus Infection

Abstract

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-γ 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.

An Increase in Herpes Simplex Virus Type 1 in the Anterior Segment of the Eye Is Linked to a Deficiency in NK Cell Infiltration in Mice Deficient in CXCR3

“…Rather, CXCR3 and CCR5 deficiency appears to impact the host response to virus infection in the nervous system ultimately resulting in efficacious or detrimental outcomes depending on the viral pathogen/disease state. [20][21][22][23][24][25] NK cells have previously been reported to be involved in the development of corneal scarring 26,27 but their control of HSV-1 replication in the eye has been questioned. 28 Specifically, the depletion of NK cells in SCID mice had no bearing on HSV-1 titers found in the cornea whereas adoptive transfer of T but not B cells significantly diminished virus replication.…”

Impaired immune responses following spinal cord injury lead to reduced ability to control viral infection

“…Mononuclear cells were obtained from whole spleen and liver at defined times using previously described methods (Stiles et al, 2006; Walsh et al, 2007). Immunophenotyping of cells was performed using the following DB Pharmingen (San Diego, CA) antibodies: fluorescein isothiocyanate (FITC)-conjugated CD45R/B220, allophycoerythrin (APC)-conjugated rat anti-mouse CD4 and CD8, APC-conjugated mouse anti-mouse NK1.1, phycoerythrin (PE)-conjugated Golden Syrian hamster anti-mouse CD3ε, FITC-conjugated rat anti-mouse CD11b, PE-conjugated rat anti-mouse CD86, and PE-conjugated rat anti-mouse I/A-I/E (MHC II) (Held et al, 2008; Trifilo et al, 2004).…”

CXCL10 and trafficking of virus-specific T cells during coronavirus-induced demyelination

“…Fluorescence-conjugated rat anti-mouse CD4 and CD8 antibodies were used to detect infiltrating CD4+ and CD8+ T cells (BD Biosciences, San Diego, CA). Additionally, polyclonal rabbit anti-mouse CXCR3 was used for primary detection of CXCR3 and FITC-conjugated goat anti-rabbit antibody was used as secondary antibody for detection (Zymed Laboratories, San Francisco, CA) [24]. In all cases, isotype-matched fluorescently conjugated antibodies were used for controls.…”