051 Loss of PDL1/L2 but not PDL1 liberates DC based priming of T cells

Skin migratory dendritic cells express high levels of PDL1 mRNA and dampen immune priming during protein immunization. However the role of the PDL1-PDL2/PD1 axis at contracting immune priming through the skin is unknown. Here we find that all skin-derived subsets of murine and human DCs, and LN resident CD11b+ classical DCs (cDC) express intermediate to high levels of the PDL1 cell surface protein. In contrast, CD8a+ LN resident DCs previously identified as critical for immunity express low levels of PDL1. High PDL1 was also identified on DCs and monocytes isolated from human melanoma metastases. To better understand the role of the PDL1/2:PD1 axis during DC based priming of T cells, we compared DC-targeted protein immunization of mice deficient in PDL1 alone or deficient in both PDL1 and PDL2. We find loss of PDL1/L2 but not PDL1 led to heightened T cell proliferation, during 4 day peptide recall. While the percentage of antigen specific CD4+ IFNg+ T cells assayed directly ex vivo by intracellular cytokine staining was unaltered in the lymph node directly draining the vaccination site of PDL1/PDL2-/- animals, in distal lymph nodes higher percentages of antigen specific T cells producing IFN-γ, IL-2 and TNF-α were identified. Collectively these data suggest that in absence of PDL1/L2 signaling, rapidly proliferating T cells exit the draining lymph node and circulate through distal nodes. Concordantly, we observe increased levels of E and P selectin binding on CD4 and CD8 T cells isolated from PDL1/2 deficient as compared to control animals. Subsequent work will examine the role of DC based PDL1/L2 signaling on the circulation and homing properties of T cells.