Antigen presentation via MHC class II by lymphatic endothelial cells dampens CD4+ T cell response (IRC7P.436)

Abstract

Abstract Lymphatic endothelial cells (LECs) can directly interact with CD8+ T cells via presentation of peptide-MHCI complexes, resulting in tolerance due to lack of costimulatory molecules and high levels of PD-L1 expression by LECs. Moreover, we and others have recently demonstrated that LECs can present peptide-MHCII complexes (pMHCII) to CD4+ T cells. However, the functional implications of antigen presentation by LECs to CD4+ T cells remain unclear. Here, we explore the tolerogenic potential of pMHCII presentation by LECs to CD4+ T cells using ovalbumin (OVA) as a model antigen. In vitro, LECs isolated from mice lacking MHCII could acquire pMHCII from wildtype dendritic cells (DCs). Subsequent LEC interactions with TCR-transgenic CD4+ T cells resulted in increased levels of CD4+ cell apoptosis, indicating deletion. Moreover, the ability of DCs to induce CD4+ T cell proliferation was decreased when LECs were present in the culture system. To examine the role of endogenous MHCII expression by LECs, we created an inducible mouse model lacking MHCII expression in LECs using a Cre-recombinase approach. In these mice, T cell responses to vaccination effects were enhanced with respect to circulating OVA-specific CD8+ T cells, indicating increased T cell help (CD4). Together, these data suggest that LEC expression of MHCII may serve to dampen or regulate immune responses. Further studies are needed to elucidate the functional role of LEC expression of MHCII in pathological conditions.