Targeting Lymph Node Niches Enhances Type 1 Immune Responses to Immunization

Summary: Generating robust CD4+ T-helper cell type 1 (Th1) responses is essential for protective vaccine-induced type 1 immunity. Here, we examine whether immunization formulation associated with enhanced vaccine efficacy promotes antigen targeting and cell recruitment into lymph node (LN) niches as...

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Main Authors: Jeffrey Lian, Aleksandra J. Ozga, Caroline L. Sokol, Andrew D. Luster
Format: Article
Language:English
Published: Elsevier 2020-05-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S221112472030632X
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spelling doaj-9420a957baf34ddb9e5d4ea8ab2984662020-11-25T03:17:49ZengElsevierCell Reports2211-12472020-05-01318Targeting Lymph Node Niches Enhances Type 1 Immune Responses to ImmunizationJeffrey Lian0Aleksandra J. Ozga1Caroline L. Sokol2Andrew D. Luster3Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Graduate Program in Immunology, Harvard Medical School, Boston, MA 02115, USACenter for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USACenter for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USACenter for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Graduate Program in Immunology, Harvard Medical School, Boston, MA 02115, USA; Corresponding authorSummary: Generating robust CD4+ T-helper cell type 1 (Th1) responses is essential for protective vaccine-induced type 1 immunity. Here, we examine whether immunization formulation associated with enhanced vaccine efficacy promotes antigen targeting and cell recruitment into lymph node (LN) niches associated with optimal type 1 responses. Immunization with antigen and Toll-like receptor agonist emulsified in oil leads to an increased differentiation of IFNγ/TNF-α+ polyfunctional Th1 cells compared to an identical immunization in saline. Oil immunization results in a rapid delivery and persistence of antigen in interfollicular regions (IFRs) of the LN, whereas without oil, antigen is distributed in the medullary region. Following oil immunization, CXCL10-producing inflammatory monocytes accumulate in the IFR, which mobilizes antigen-specific CD4+ T cells into this niche. In this microenvironment, CD4+ T cells are advantageously positioned to encounter arriving IL-12-producing inflammatory dendritic cells (DCs). These data suggest that formulations delivering antigen to the LN IFR create an inflammatory niche that can improve vaccine efficacy.http://www.sciencedirect.com/science/article/pii/S221112472030632Xvaccinesemulsificationlymph nodeinterfollicular regionchemokinesCXCL10
collection DOAJ
language English
format Article
sources DOAJ
author Jeffrey Lian
Aleksandra J. Ozga
Caroline L. Sokol
Andrew D. Luster
spellingShingle Jeffrey Lian
Aleksandra J. Ozga
Caroline L. Sokol
Andrew D. Luster
Targeting Lymph Node Niches Enhances Type 1 Immune Responses to Immunization
Cell Reports
vaccines
emulsification
lymph node
interfollicular region
chemokines
CXCL10
author_facet Jeffrey Lian
Aleksandra J. Ozga
Caroline L. Sokol
Andrew D. Luster
author_sort Jeffrey Lian
title Targeting Lymph Node Niches Enhances Type 1 Immune Responses to Immunization
title_short Targeting Lymph Node Niches Enhances Type 1 Immune Responses to Immunization
title_full Targeting Lymph Node Niches Enhances Type 1 Immune Responses to Immunization
title_fullStr Targeting Lymph Node Niches Enhances Type 1 Immune Responses to Immunization
title_full_unstemmed Targeting Lymph Node Niches Enhances Type 1 Immune Responses to Immunization
title_sort targeting lymph node niches enhances type 1 immune responses to immunization
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2020-05-01
description Summary: Generating robust CD4+ T-helper cell type 1 (Th1) responses is essential for protective vaccine-induced type 1 immunity. Here, we examine whether immunization formulation associated with enhanced vaccine efficacy promotes antigen targeting and cell recruitment into lymph node (LN) niches associated with optimal type 1 responses. Immunization with antigen and Toll-like receptor agonist emulsified in oil leads to an increased differentiation of IFNγ/TNF-α+ polyfunctional Th1 cells compared to an identical immunization in saline. Oil immunization results in a rapid delivery and persistence of antigen in interfollicular regions (IFRs) of the LN, whereas without oil, antigen is distributed in the medullary region. Following oil immunization, CXCL10-producing inflammatory monocytes accumulate in the IFR, which mobilizes antigen-specific CD4+ T cells into this niche. In this microenvironment, CD4+ T cells are advantageously positioned to encounter arriving IL-12-producing inflammatory dendritic cells (DCs). These data suggest that formulations delivering antigen to the LN IFR create an inflammatory niche that can improve vaccine efficacy.
topic vaccines
emulsification
lymph node
interfollicular region
chemokines
CXCL10
url http://www.sciencedirect.com/science/article/pii/S221112472030632X
work_keys_str_mv AT jeffreylian targetinglymphnodenichesenhancestype1immuneresponsestoimmunization
AT aleksandrajozga targetinglymphnodenichesenhancestype1immuneresponsestoimmunization
AT carolinelsokol targetinglymphnodenichesenhancestype1immuneresponsestoimmunization
AT andrewdluster targetinglymphnodenichesenhancestype1immuneresponsestoimmunization
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