T Cell Co-stimulation and Functional Modulation by Innate Signals

Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs), play a pivotal role in the initiation of innate immune responses. Certain PRRs are also expressed by CD4(+) and CD8(+) T cells, where they function to provide co-stimulatory signals for their activation and differentiation. Recently, stimulator of interferon genes (STING) was found to be highly expressed in CD4(+) and CD8(+) T cells and to modulate T cell function. STING signaling inhibits cell growth and stimulates type I interferon (IFN-I) responses in T cells through reciprocal regulation between T cell receptor (TCR) and STING signals. Here, we propose a model whereby innate signals by TLRs and STING regulate TCR signals and T cell functions.