T Cell/B Cell Interactions in the Establishment of Protective Immunity.

Julia Ritzau-Jost,Andreas Hutloff

doi:10.3390/vaccines9101074

Julia Ritzau-Jost, Andreas Hutloff

Open Access

https://doi.org/10.3390/vaccines9101074

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Abstract

Follicular helper T cells (Tfh) are the T cell subset providing help to B cells for the generation of high-affinity antibodies and are therefore of key interest for the development of vaccination strategies against infectious diseases. In this review, we will discuss how the generation of Tfh cells and their interaction with B cells in secondary lymphoid organs can be optimized for therapeutic purposes. We will summarize different T cell subsets including Tfh-like peripheral helper T cells (Tph) capable of providing B cell help. In particular, we will highlight the novel concept of T cell/B cell interaction in non-lymphoid tissues as an important element for the generation of protective antibodies directly at the site of pathogen invasion.

Highlights

Vaccination strategies against infectious diseases are typically based on the generation of long-lived high-affinity antibodies, which are capable of combating pathogens in multiple mechanisms
CAF01 promotes germinal centres (GC) responses and prolonged humoral responses in murine neonates, strong Th1/Th17 responses in mice clinical trials chemically modified cyclic dinucleotide induces Tfh and Th1 cell responses in neonatal cord blood, three-dose vaccination schedule is beneficial in mice leading to higher antibody titres; presence of cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) within HIV-derived virus-like particles enhanced adaptive immune responses, increased Tfh cell numbers in draining lymphnode
Tfh cells are a key determinant for the generation of high-affinity memory B cells and plasma cells

Summary

Introduction

Vaccination strategies against infectious diseases are typically based on the generation of long-lived high-affinity antibodies, which are capable of combating pathogens in multiple mechanisms. A specific cytokine milieu at the T/B border further promotes Tfh cell differentiation This region is rich in a special subpopulation of IL-2Rhigh DCs, which act as a molecular sink for IL-2 [31]. Activated B cells, which highly express IL-2Rα, contribute to the low IL2 levels at the T/B border and provide additional specific signals for further Tfh cell development, since mature Tfh cells are not generated in the absence of B cells [29]. Dependent on received Tfh cell-mediated signals, GC B cells either undergo further rounds of somatic hypermutation to increase BCR affinity or leave the germinal centre to differentiate into long-lived antibody-producing PCs or memory B cells. Classical Tfh cells are generated in SLO, whereas in non-lymphoid tissues, Tph cells are typically the population providing help for the local differentiation of B cells into plasma cells.

Circulating

T and B Cells in Inflamed Tissues

Vaccination Strategies to Promote Tfh Cell Development

Literature alum

Literature

Conclusions