Naive CD4+ T cells synthesize a hyaluronan-rich glycocalyx that is diminished following activation.

Hyaluronan (HA) is a key component of the pericellular and extracellular matrix and is synthesized by both non-hematopoietic and myeloid cells. In this study, we demonstrate that adaptive immune T cells not only respond to exogenously added high-molecular-weight HA by reducing proliferation but also generate an endogenous HA-rich glycocalyx in a stage-specific manner, as shown by fluorescence assisted carbohydrate electrophoresis and imaging studies. HA in the glycocalyx of naive CD4+ T cells, localized with the HA-binding proteoglycan, versican (VCAN). During differentiation into effector subsets, pericellular HA/VCAN is removed, with HA detected intracellularly, often co-localized with CD44. Hyaluronan synthase 3 (HAS3) is the predominant enzyme in naive CD4+ T cells, as HAS3-deficient T cells display minimal surface HA and exhibit extensive proliferation. We discuss the significance of the metabolic turnover of the HA/VCAN glycocalyx in T cells as a mechanism to regulate activation and proliferation.