Endogenous Galectin-1 Induced By Activated Cd8 T Cells Limits Cd8 Burst Size

CD8 burst size is regulated by the balanced control of CD8 activation, expansion, and apoptosis. While it is clear the length of antigen exposure and continued and sustained TCR signaling regulate these processes, molecular regulators controlling this balance are not well elucidated. Here, we report that galectin‐1 (gal‐1) deficient CD8 cells hyper‐proliferated upon TCR engagement. Dividing gal‐1 deficient CD8 cells were less susceptible to apoptosis, suggesting gal‐1 promotes apoptosis to limit burst size. Coinciding with induced expression of gal‐1 in CD8 cells within 48 hours of activation, TCR signaling was sustained in gal‐1 deficient CD8 cells over that period, reflected in more pERK and pS59 lck, and less lck‐associated SHP‐1. Consistently, treatment of gal‐1 deficient CD8 cells with recombinant gal‐1 antagonized sustained pERK. These data suggest gal‐1 may regulate burst size through antagonism of continued TCR signaling by modulating the ERK positive/SHP‐1 negative feedback pathways. Adoptive transfer of gal‐1 deficient TCR transgenic cells into wild type hosts indicates autocrine CD8 gal‐1 production is responsible for limiting CD8 expansion in vivo . These findings identify gal‐1 as a novel negative regulator of CD8 burst size, which functions by opposing continued TCR signaling and promoting apoptosis. Supported by NIH RO1A1056155 to M. C. Miceli, T32 AI07323‐15, AI07126‐30, and Warsaw Fellowship to S. D. Liu.