Abstract

Afferent lymphatic vessels contribute to immunity by transporting antigen and leukocytes to draining lymph nodes (LNs) and are emerging as new players in the regulation of peripheral tolerance. Performing intravital microscopy in inflamed murine ear skin we found that migrating dendritic cells (DCs) and antigen-experienced effector T cells spend considerable time arresting or clustering within afferent lymphatic capillaries. We also observed that intralymphatic T cells frequently interacted with DCs. When imaging polyclonal T cells during an ongoing contact-hypersensitivity response, most intralymphatic DC-T cell interactions were short-lived. Conversely, during a delayed-type-hypersensitivity response, cognate antigen-bearing DCs engaged in long-lived MHCII-(I-A/I-E)-dependent interactions with antigen-specific T cells. Long-lived intralymphatic DC-T cell interactions reduced the speed of DC crawling but did not delay overall DC migration to draining LNs. While further consequences of these intralymphatic interactions still need to be explored, our findings suggest that lymphatic capillaries represent a unique compartment in which adaptive immune interaction and modulation occur.

Highlights

  • Afferent lymphatic vessels are present within most vascularized tissues and functionally convey lymph toward and into a draining lymph nodes (LNs)

  • Imaging was performed in the ear skin of VE-cadherin-Cre × RFP mice, which feature red-fluorescent blood and lymphatic vessels [7], either upon adoptive transfer of LPS-matured YFP+ bone marrow-derived dendritic cells (DCs) (BM-DCs; Figure 1A), or upon reconstitution of these mice with bone marrow from CD11c-YFP mice (BM chimeras, Figure 1B)

  • In this study we have used intravital microscopy to further detail the behavior of DCs and T cells within dermal lymphatic capillaries during an ongoing immune response

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Summary

Introduction

Afferent lymphatic vessels are present within most vascularized tissues and functionally convey lymph toward and into a draining LN. The main cell types migrating via afferent lymphatic vessels are antigen-experienced CD4+ T cells and antigen-presenting dendritic cells (DCs) [3, 4]. While T cell recirculation through afferent lymphatic vessels is thought to contribute to immunesurveillance, DC migration is important for maintenance of tolerance and for induction of protective immunity in draining LNs [3]. In this regard, DCs within the tissue take up antigen and migrate via afferent lymphatic vessels to a draining LN.

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