The co-stimulatory effects of MyD88-dependent toll-like receptor signaling on activation of murine γδ T Cells

Jinping Zhang, Jia Wang, Lan Pang, Guorui Xie, Thomas Welte, Vandana Saxena, Jason Wicker, Brian Mann, Lynn Soong, Alan Barrett, Willi Born, Rebecca O'Brien, Tian Wang

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12 Scopus citations

Abstract

γδ T cells express several different toll-like receptor (TLR)s. The role of MyD88-dependent TLR signaling in TCR activation of murine γδ T cells is incompletely defined. Here, we report that Pam3CSK4 (PAM, TLR2 agonist) and CL097 (TLR7 agonist), but not lipopolysaccharide (TLR4 agonist), increased CD69 expression and Th1-type cytokine production upon anti-CD3 stimulation of γδ T cells from young adult mice (6-to 10-week-old). However, these agonists alone did not induce γδ T cell activation. Additionally, we noted that neither PAM nor CL097 synergized with anti-CD3 in inducing CD69 expression on γδ T cells of aged mice (21-to 22-month-old). Compared to young γδ T cells, PAM and CL097 increased Th-1 type cytokine production with a lower magnitude from anti-CD3-stimulated, aged γδ T cells. Vγ1+and Vγ4+cells are two subpopulations of splenic γδ T cells. PAM had similar effects in anti-CD3-Activated control and Vγ4+subset-depleted γδ T cells; whereas CL097 induced more IFN-γ production from Vγ4+subset-depleted γδ T cells than from the control group. Finally, we studied the role of MyD88-dependent TLRs in γδ T cell activation during West Nile virus (WNV) infection. γδ T cell, in particular, Vγ1+subset expansion was significantly reduced in both MyD88-And TLR7-deficient mice. Treatment with TLR7 agonist induced more Vγ1+cell expansion in wild-type mice during WNV infection. In summary, these results suggest that MyD88-dependent TLRs provide co-stimulatory signals during TCR activation of γδ T cells and these have differential effects on distinct subsets.

Original languageEnglish (US)
Article numberA1350
JournalPloS one
Volume9
Issue number9
DOIs
StatePublished - Sep 18 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Zhang, J., Wang, J., Pang, L., Xie, G., Welte, T., Saxena, V., Wicker, J., Mann, B., Soong, L., Barrett, A., Born, W., O'Brien, R., & Wang, T. (2014). The co-stimulatory effects of MyD88-dependent toll-like receptor signaling on activation of murine γδ T Cells. PloS one, 9(9), [A1350]. https://doi.org/10.1371/journal.pone.0108156