Effector CD8 T cells possess suppressor function after 4-1BB and Toll-like receptor triggering

AUTOR(ES)

Myers, Lara

FONTE

The National Academy of Sciences

RESUMO

To better understand how innate and adaptive immune responses interact with each other, we combined 4-1BB T cell costimulation with specific adjuvants to determine whether these treatments would influence specific T cell expansion and function in vivo. In the presence of 4-1BB ligation and Toll-like receptor 3 (TLR)3 and/or TLR4 triggering, CD8 T cell clonal expansion and survival was augmented profoundly. Specific T cells primed in vivo with TLR ligands responded normally to in vitro recall stimulus, but, surprisingly, copriming with 4-1BB costimulation significantly impaired the recall response even though many more specific effector T cells were rescued in vivo. Here, we demonstrate that the rescued CD8 T cells suppressed CD4 T cell proliferation via a type β transforming growth factor-dependent mechanism. Thus, 4-1BB and TLR ligands induce survival of specific effector CD8 T cells with suppressive recall potential, which may explain the dual role that 4-1BB activation plays in mediating tumor clearance and prevention of autoimmune disease.

Documentos Relacionados

• Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling–dependent CD8 T-cell activation
• Toll-like receptor 4 (TLR4) na modulação da imunidade do tipo 2.
• Helicobacter pylori Activates Toll-Like Receptor 4 Expression in Gastrointestinal Epithelial Cells
• Toll-Like Receptor 4-Dependent Activation of Dendritic Cells by a Retrovirus
• Murine retroviruses activate B cells via interaction with toll-like receptor 4