Abstract

Mesenchymal stem cells (MSC) possess a wide range of immunosuppressive functions. Among these is the ability to inhibit CD4+ T cell proliferation. Dendritic cells (DC) play a role in initiating cell-mediated immunity; however, the immunosuppressive influence of MSC on professional antigen presenting cells remains unclear. DC exposed to TNF- and cultured with murine MSC failed to show regular upregulation of maturation markers. Similarly, the presence of MSC abrogated the capacity of ovalbumin-pulsed DC to support antigen specific CD4+ T cell proliferation, or for DC to display an MHC class II- peptide complex recognizable by specific antibody. Interestingly, culture of MSC with DC resulted in reduced expression of CCR7 by DC following stimulation. Likewise, DC matured in the presence of MSC, showed significantly less migration to CCL19. In contrast, murine MSC prevented loss of expression of the tissue anchoring protein E-cadherin by DC. Modulation of DC maturation and function was not permanent and could be restored after removal of MSC. These data demonstrate that MSC modulate the three cardinal features of DC maturation, providing the first demonstration of MSC interference with DC migration