Multiplex Static and Dynamic Imaging Reveals the Role of Lymphatic Sinus-Associated Dendritic Cells in Inducing Immunity to Particulate Antigens

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIAID	IMMUNO-8

* FARE Award Winner

Authors

• MY Gerner
• RN Germain

Abstract

Seconds after immunization, small protein antigens (Ags) are delivered via the lymphatics into draining lymph nodes (dLNs) and are efficiently taken up by LN-resident dendritic cells (DCs) directly sampling small proteins (<70kDa) from the LN conduits. This leads to Ag presentation, and to T cell clonal expansion and effector differentiation. In contrast, particulate Ags (bacteria, viruses, and particle-based vaccines) are not thought to passively drain to dLNs due to inefficient lymphatic vessel entry in the periphery. Instead, it is thought that only the peripheral tissue DCs migrating to the dLN days after the initiation of infection present Ag and activate T cells. By utilizing confocal and multi-photon imaging, we demonstrate that large particulates, including particle-based vaccines and bacteria, do in fact rapidly drain to the dLN, where they are immediately sampled by a population of LN-resident DCs lining the lymphatic sinuses (LS) and extending highly motile dendrites directly into the LS lumen. Importantly, these DCs efficiently induce very rapid CD4 T cell activation and effector differentiation. Thus, the lymphatic architecture is designed for rapid communication with the LN innate sensory cells, which during infection of peripheral tissues allows for a prompt generation of adaptive immunity independent of Ag size.

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