CCL22 impedes T cell activation capacities of dendritic cells by reducing membrane expression of MHC molecules and CD80

The chemokine CCL22 is a well known modulator of immune responses. By binding to its receptor CCR4, which is highly expressed on several T cell subtypes as well as dendritic cells (DC), CCL22 mediates chemotaxis of responsive cells, thus influencing the distribution of these cells within tissues. For instance, CCL22 is known to be expressed in human and murine tumors contributing to the recruitment of regulatory T cells. Given that many chemokines show effects exceeding pure chemotaxis we hypothesized that CCL22 mediates modulation of immune responses by further activities. In order to identify additional immune modulating properties of CCL22 on DCs and T cells we stimulated murine splenocytes isolated from healthy donor mice with recombinant CCL22 in vitro . We did not find any significant alteration in expression of cell surface activation markers like CTLA-4, PD-1 or CD62L on CD4 + , CD8 + and FoxP3 + T cells. However, splenic CD11c + DCs showed a significant reduction in MHC class I molecules on cell surface upon stimulation with CCL22. Notably, this reduction was most prominent in CD11c + CD8α + DCs which also showed decreased levels of MHC class II molecules as well as the costimulatory receptor CD80 after encountering CCL22. In summary, our data indicate an alternative mode of action for CCL22 on Dendritic cells, especially on CD11c + CD8α + DCs. The CCL22-mediated modification of DC’s capabilities to present antigens and to activate T cells might represent a fine-tuning mechanism of adaptive immune responses.