Vaccine Designs Utilizing Invariant NKT-Licensed Antigen-Presenting Cells Provide NKT or T Cell Help for B Cell Responses.

Shin-Ichiro Fujii,Yusuke Sato,Kanako Shimizu,Satoru Yamasaki

doi:10.3389/fimmu.2018.01267

Shin-Ichiro Fujii, Yusuke Sato + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2018.01267

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Abstract

Vaccines against a variety of infectious diseases have been developed and tested. Although there have been some notable successes, most are less than optimal or have failed outright. There has been discussion about whether either B cells or dendritic cells (DCs) could be useful for the development of antimicrobial vaccines with the production of high titers of antibodies. Invariant (i)NKT cells have direct antimicrobial effects as well as adjuvant activity, and iNKT-stimulated antigen-presenting cells (APCs) can determine the form of the ensuing humoral and cellular immune responses. In fact, upon activation by ligand, iNKT cells can stimulate both B cells and DCs as via either cognate or non-cognate help. iNKT-licensed DCs generate antigen-specific follicular helper CD4+ T cells, which in turn stimulate B cells, thus leading to long-term antigen-specific antibody production. Follicular helper iNKT cell-licensed B cells generally produce rapid, but short-term antibody. However, under some conditions in the presence of Th cells, the antibody production can be prolonged. With regards to humoral immunity, the quality and quantity of Ab produced depends on the APC type and the form of the vaccine. In terms of cellular immunity and, in particular, the induction of cytotoxic CD8+ T cells, iNKT-licensed DCs show prominent activity. In this review, we discuss differences in iNKT-stimulated APC types and the quality of the ensuing immune response, and also discuss their application in vaccine models to develop successful preventive immunotherapy against infectious diseases.

Highlights

The success of vaccination strategies against viral infection or cancer depends on the efficient gene ration of appropriate antigen-specific T and B cell responses
T-dependent responses are typically induced by protein antigens and, as the term implies, there is cognate T-cell help for the antigen-specific B cells [3], which is provided by a specialized subset of CD4+ T cells called T follicular helper (Tfh) cells
The activated B cells are recruited to the border of the T cell and B cell zones, in which Tfh cells are generated following interacting with dendritic cells (DCs) presenting the same antigen

Summary

INTRODUCTION

The success of vaccination strategies against viral infection or cancer depends on the efficient gene ration of appropriate antigen-specific T and B cell responses. Adequate antibody (Ab) responses of appropriate specificity elicited by vaccination are required to control and protect against many viral pathogens, such as influenza, human immunodeficiency virus, and human papilloma virus [1]. By upregulating CXCR5, Tfh cells in turn localize to the boundary of the T and B cell zone [3], which is critical location for B cells to encounter Tfh cells Besides these classical T-dependent and T-independent vac cines, NKT cell-mediated vaccines have been tested as a third vaccine candidate. We discuss how these two pathways, i.e., vaccines utilizing iNKT cell help for B cells or iNKT cell help for DCs, augment efficient antigen-specific Ab production in the development of vaccination strategies against infectious diseases

THE ROLE OF iNKT CELLS IN INFECTIOUS DISEASES

Findings

CONCLUSION