B7-H7 (HHLA2) inhibits T-cell activation and proliferation in the presence of TCR and CD28 signaling

摘要

Modulation of T-cell responses has played a key role in treating cancers and autoimmune diseases.Therefore,understanding how different receptors on T cells impact functional outcomes is crucial.The influence of B7-H7(HHLA2)and CD28H(TMIGD2)on T-cell activation remains controversial.Here we examined global transcriptomic changes in human T cells induced by B7-H7.Stimulation through TCR with OKT3 and B7-H7 resulted in modest fold changes in the expression of select genes;however,these fold changes were significantly lower than those induced by OKT3 and B7-1 stimulation.The transcriptional changes induced by OKT3 and B7-H7 were insufficient to provide functional stimulation as measured by evaluating T-cell proliferation and cytokine production.Interestingly,B7-H7 was coinhibitory when simultaneously combined with TCR and CD28 stimulation.This inhibitory activity was comparable to that observed with PD-L1.Finally,in physiological assays using T cells and APCs,blockade of B7-H7 enhanced T-cell activation and proliferation,demonstrating that this ligand acts as a break signal.Our work defines that the transcriptomic changes induced by B7-H7 are insufficient to support full costimulation with TCR signaling and,instead,B7-H7 inhibits T-cell activation and proliferation in the presence of TCR and CD28 signaling.