Hyaluronan binding identifies the most proliferative activated and memory T cells

CD44 is expressed on T cells where its ability to bind hyaluronan is tightly regulated. Here, we investigated when T cells bind hyaluronan during an immune response. We found that naive, murine T cells do not bind fluoresceinated hyaluronan but are induced to bind upon antigen-induced T-cell activation in vitro and in vivo. Hyaluronan binding occurred on proliferating T cells and the percentage of hyaluronan-binding cells correlated with the strength of the activation stimulus. A small percentage of hyaluronan-binding cells persisted after in vitro activation and had a memory phenotype (CD122+CD44hi). This hyaluronan-binding population increased after culture with IL-7 or IL-15 and proliferated more rapidly than nonbinding cells. In vivo, approximately 20–30% of antigen-specific OT-I CD8+ memory T cells in the spleen and BM bound hyaluronan. Hyaluronan binding identified memory cells that proliferated faster in IL-7 and IL-15, and enriched for CD62L+ central memory cells. In vivo homeostatic proliferation induced hyaluronan binding on a small percentage of the most rapidly dividing cells after several cell divisions. This study demonstrates that hyaluronan binding is induced upon antigen-induced T-cell activation and occurs on a percentage of the most proliferative activated and memory T cells.