title: The co-stimulatory effects of MyD88-dependent Toll-like receptor signaling on activation of murine γδ T cells.
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.
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Jinping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Lan
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Guorui
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Welte
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Vandana
authors.initials: V
authors.lastname: Saxena
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Wicker
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Mann
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Lynn
authors.initials: L
authors.lastname: Soong
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Alan
authors.initials: A
authors.lastname: Barrett
authors.affiliation: Integrated Department of Immunology, National Jewish Health Center, Denver, Colorado, United States of America.
authors.forename: Willi
authors.initials: W
authors.lastname: Born
authors.affiliation: Integrated Department of Immunology, National Jewish Health Center, Denver, Colorado, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: O'Brien
authors.affiliation: Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors