V gamma 4+ T cells regulate host immune response to West Nile virus infection

• Published in: FEMS immunology and medical microbiology 2011-11, Vol.63 (2), p.183-192
• Main Authors: Welte, Thomas, Aronson, Judith, Gong, Bin, Rachamallu, Aparna, Mendell, Nicole, Tesh, Robert, Paessler, Slobodan, Born, Willi K, O'Brien, Rebecca L, Wang, Tian
• Format: Article
• Language: English
• Subjects: Brain; Cell proliferation; Encephalitis; Immunity; Infection; Inflammation; Interleukin 10; Interleukin 17; Lymphocytes T; Spleen; Transforming growth factor- beta; Viremia; West Nile virus
• ISSN: 0928-8244; 1574-695X
• DOI: 10.1111/j.1574-695X.2011.00840.x

The V gamma 4+ cells, a subpopulation of peripheral gamma delta T cells, are involved in West Nile virus (WNV) pathogenesis, but the underlying mechanism remains unclear. In this study, we found that WNV-infected V gamma 4+ cell-depleted mice had lower viremia and a reduced inflammatory response in the brain. The V gamma 4+ cells produced IL-17 during WNV infection, but blocking IL-17 signaling did not affect host susceptibility to WNV encephalitis. We also noted that there was an enhanced magnitude of protective splenic V gamma 1+ cell expansion in V gamma 4+ cell-depleted mice compared to that in controls during WNV infection. In addition, V gamma 4+ cells of WNV-infected mice had a higher potential for producing TGF- beta . The gamma delta T cells of WNV-infected V gamma 4+ cell-depleted mice had a higher proliferation rate than those of WNV-infected controls upon ex vivo stimulation with anti-CD3, and this difference was diminished in the presence of TGF- beta inhibitor. Finally, V gamma 4+ cells of infected mice contributed directly and indirectly to the higher level of IL-10, which is known to play a negative role in immunity against WNV infection. In summary, V gamma 4+ cells suppress V gamma 1+ cell expansion via TGF- beta and increase IL-10 level during WNV infection, which together may lead to higher viremia and enhanced brain inflammation.