Targeting the gut vascular endothelium induces gut effector CD8 T cell responses via cross-presentation by dendritic cells
- Author(s)
- Bourges, D; Zhan, YF; Brady, JL; Braley, H; Caminschi, I; Prato, S; Villadangos, JA; Lew, AM;
- Details
- Publication Year 2007-11-01,Volume 179,Issue #9,Page 5678-5685
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Systemic delivery of Ag usually induces poor mucosal immunity. To improve the CD8 T cell response at mucosal sites, we targeted the Ag to MAdCAM-1, a mucosal addressin cell adhesion molecule expressed mainly by high endothelial venules (HEV) in mesenteric lymph nodes (MLN) and Peyer's patches of gut-associated lymphoid tissue. When chemical conjugates of antiMAdCAM-1 Ab and model Ag OVA were injected i.v., a greatly enhanced proliferative response of Ag-specific OT-I CD8 T cells was detected in MLN. This was preceded by prolonged accumulation, up to 2 wk, of the anti-MAdCAM OVA conjugate on HEV of Peyer's patches and MLN. In contrast, nontargeted OVA conjugate was very inefficient in inducing OT-I CD8 T cell proliferation in MLN and required at least 20-fold more Ag to induce a comparable response. In addition, MAdCAM targeting elicits an endogenous OVA-specific CD8 T cell response, evident by IFN-gamma production and target killing. Induced response offers protection against an OVA-expressing B cell lymphoma. We propose that the augmentation of gut CD8 T cell responses by MAdCAM targeting is due to both accumulation of Ag in the HEV and conversion of a soluble Ag to a cell-associated one, allowing cross-presentation by Ms.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- CLONAL EXPANSION; MUCOSAL IMMUNITY; LYMPH-NODE; IN-VIVO; ANTIGEN; ADDRESSIN; DELIVERY; MOUSE; DIFFERENTIATION; TRAFFICKING
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Creation Date: 2007-11-01 12:00:00