Fig. 1.

Interaction of TLR and TCR signaling pathways in T cells. Activation of naïve CD4 + and CD8 + T cells is initiated by recognition of the TCR and MHC/peptide complex. TCR signaling is transmitted by the CD3 molecule and then i.a. activates the PI3K/Akt/mTOR pathway, leading to the reprogramming of energy metabolism and activation of transcription factors, such as NF-κB, NFAT, and AP1. These transcription factors control the differentiation of T cells, the downstream production of cytokines, and upregulate the expression of TLRs (left panel). In the activated T cells, engagement of TLR agonists and TLRs initiates downstream signal cascades by recruiting adaptor proteins such as MyD88 or TRIF, leading to enhanced activation of PI3K/Akt/mTOR pathway, upregulated energy metabolism, and activates the transcription factors such as NF-κB and IRF4 to regulate the production of proinflammatory cytokines and chemokines (right panel). TLRs expressed in CD4 + and CD8 + T cells serve as costimulatory molecules in enhancing TCR signal-induced T-cell activation and function survival