Role of CD8⁺T Cells in Control of West Nile Virus Infection

Abstract

Infection with West Nile virus (WNV) causes fatal encephalitis more frequently in immunocompromised humans than in those with a healthy immune system. Although a complete understanding of this increased risk remains unclear, experiments with mice have begun to define how different components of the adaptive and innate immune response function to limit infection. Previously, we demonstrated that components of humoral immunity, particularly immunoglobulin M (IgM) and IgG, have critical roles in preventing dissemination of WNV infection to the central nervous system. In this study, we addressed the function of CD8 ؉ T cells in controlling WNV infection. Mice that lacked CD8 ؉ T cells or classical class Ia major histocompatibility complex (MHC) antigens had higher central nervous system viral burdens and increased mortality rates after infection with a low-passage-number WNV isolate. In contrast, an absence of CD8 ؉ T cells had no effect on the qualitative or quantitative antibody response and did not alter the kinetics or magnitude of viremia. In the subset of CD8؉ -T-cell-deficient mice that survived initial WNV challenge, infectious virus was recovered from central nervous system compartments for several weeks. Primary or memory CD8؉ T cells that were generated in vivo efficiently killed target cells that displayed WNV antigens in a class I MHC-restricted manner. Collectively, our experiments suggest that, while specific antibody is responsible for terminating viremia, CD8 ؉

A live, attenuated recombinant West Nile virus vaccine

“…CD8 ϩ T cells play a crucial role in recovery from WNV infection (26). In the clinical trial, we detected WN virus-specific T-cell responses in 93% and 100% of subjects inoculated with ChimeriVax-WN02 5.0 log and 3.0 log, respectively, whereas a low number of IFN-␥-producing T cells to WN virus peptides was found in only one of five and T lymphocyte proliferative responses in three of five YF-VAX recipients.…”

West Nile virus meningoencephalitis

“…In mice, IFN-/ , B cells and antibody, complement, and CD8 + T cells, all have crucial roles in the control of WNV infection. 23,[41][42][43][44] In addition, secretion by WNV-infected neurons of the chemokine CXCL10 facilitates recruitment of CD8 + T cells to the CNS. 45,46 WNV infection leads to activation of Tlr3, which recognizes viral double-stranded RNA.…”

CXCR3 Mediates Region-Specific Antiviral T Cell Trafficking within the Central Nervous System during West Nile Virus Encephalitis

“…Rat polyclonal Abs against WNV Ag have been described in detail elsewhere (51), and unconjugated rabbit polyclonal Abs against CXCR3 (Zymed Laboratories), BrdU (Roche), and Alexa Fluor-conjugated secondary Abs (Invitrogen: Molecular Probes) were purchased commercially. For flow cytometry, fluorescently conjugated Abs against CD3, CD4, CD8, NK1.1, and IFN-␥ were purchased from BD Pharmingen.…”