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

Research output: Contribution to journalArticle

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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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T-cells
Toll-Like Receptors
T-lymphocytes
Chemical activation
T-Lymphocytes
mice
Pulse amplitude modulation
agonists
West Nile virus
T-Lymphocyte Subsets
Virus Diseases
Viruses
Toll-like receptors
Cytokines
cytokines
Lipopolysaccharides
Young Adult
young adults
infection
lipopolysaccharides

ASJC Scopus subject areas

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

Cite this

The co-stimulatory effects of MyD88-dependent toll-like receptor signaling on activation of murine γδ T Cells. / Zhang, Jinping; Wang, Jia; Pang, Lan; Xie, Guorui; Welte, Thomas; Saxena, Vandana; Wicker, Jason; Mann, Brian; Soong, Lynn; Barrett, Alan; Born, Willi; O'Brien, Rebecca; Wang, Tian.

In: PLoS One, Vol. 9, No. 9, A1350, 18.09.2014.

Research output: Contribution to journalArticle

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, vol. 9, no. 9, A1350. https://doi.org/10.1371/journal.pone.0108156
Zhang, Jinping ; Wang, Jia ; Pang, Lan ; Xie, Guorui ; Welte, Thomas ; Saxena, Vandana ; Wicker, Jason ; Mann, Brian ; Soong, Lynn ; Barrett, Alan ; Born, Willi ; O'Brien, Rebecca ; Wang, Tian. / The co-stimulatory effects of MyD88-dependent toll-like receptor signaling on activation of murine γδ T Cells. In: PLoS One. 2014 ; Vol. 9, No. 9.
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