Antigen presentation via intravascular extensions of renal DC is necessary for antigen-specific T Cell migration into the kidney

Abstract

We have previously shown that CX3CR1+ renal DC sample antigen via intravascular processes in the context of systemic infection and immune complex disease. Here, we investigated the role of intravascular DC processes in antigen presentation and effector T cell migration to the kidney. To investigate T cell migration, CFP-OVA E. coli and CD8+ DsRed+ OT-I effector T cells, pretreated with Pertussis toxin (PTX), were i.v. injected into CX3CR1gfp/+ mice 24h before 2P intravital microscopy (2PIM) of the kidney was performed. OT-I T cells migrated into the kidney, with 2PIM showing prolonged (30 min) DC-T cell interactions. OT-I migration was significantly higher (2-fold) when OVA was present (CFP-OVA E. coli vs WT E.coli), demonstrating that migration of effector T cells was antigen-specific. To test if antigen presentation by DC was necessary to mediate migration of T cells, we used CD11c-YFP Kb−/− bone marrow chimeric recipients (hematopoietic cells lack H-2k(b), parenchymal cells express H-2k(b)). CFP-OVA E. coli injection into a CD11c YFP Kb−/− bone marrow chimeric mouse abrogated effector OT-I T cell migration into the renal tissue. Our data demonstrate that migration of effector T cells in the setting of systemic infection is antigen-specific. In addition, antigen presentation by hematopoietic cells, most likely DC, is necessary to mediate antigen-specific effector T cell migration. H-2k(b) expression on parenchymal and endothelial cells does not mediate antigen-specific effector T cell migration. Our findings show that renal DC have two roles: immune surveillance by sampling and presenting antigen via intravascular processes, and guiding effector T cells to the site of antigen.