Role of CD44 and hyaluronic acid (HA) in activation of alloreactive and antigen-specific T cells by bone marrow-derived dendritic cells

In the current study, the role played by hyaluronic acid (HA) and its receptor CD44 on the activation and functions of dendritic cells (DCs) was investigated. Activation of DCs with HA enhanced their ability to stimulate allogeneic and antigen (Ag)-specific T cells markedly. HA treatment upregulated the expression of costimulatory molecules such as CD40, CD80, and CD86 on DCs. Cell mixing experiments using DC or T cells from CD44 wild-type or CD44 knockout mice as well as blocking studies with anti-CD44 monoclonal antibodies revealed that CD44 expression on T cells but not DC played a critical role in Ag-specific T-cell responsiveness. Also, the HA-induced activation of DC was independent of CD44. When conjugate formation between Ag-pulsed DCs and Ag-specific T cells was studied, the deficiency of CD44 on T cells rather than on DCs was found to play a key role in T-cell-DC interaction. Together, these data demonstrated that HA can activate DC independently of CD44; however, CD44 expressed on Ag-specific T cells plays a critical role in its interaction with DC and resultant expansion of T cells.