The co-stimulatory effects of MyD88-dependent Toll-like receptor signaling on activation of murine ?? T cells.

ABSTRACT: ?? T cells express several different toll-like receptor (TLR)s. The role of MyD88- dependent TLR signaling in TCR activation of murine ?? 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 ?? T cells from young adult mice (6-to 10-week-old). However, these agonists alone did not induce ?? T cell activation. Additionally, we noted that neither PAM nor CL097 synergized with anti-CD3 in inducing CD69 expression on ?? T cells of aged mice (21-to 22-month-old). Compared to young ?? T cells, PAM and CL097 increased Th-1 type cytokine production with a lower magnitude from anti-CD3- stimulated, aged ?? T cells. V?1+ and V?4+ cells are two subpopulations of splenic ?? T cells. PAM had similar effects in anti-CD3-activated control and V?4+ subset- depleted ?? T cells; whereas CL097 induced more IFN-? production from V?4+ subset-depleted ?? T cells than from the control group. Finally, we studied the role of MyD88-dependent TLRs in ?? T cell activation during West Nile virus (WNV) infection. ?? T cell, in particular, V?1+ subset expansion was significantly reduced in both MyD88- and TLR7- deficient mice. Treatment with TLR7 agonist induced more V?1+ 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 ?? T cells and these have differential effects on distinct subsets.

SUBMITTER: Zhang J 

PROVIDER: S-EPMC4169491 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature