IL-4-Producing Vγ1+/Vδ6+ γδ T Cells Sustain Germinal Center Reactions in Peyer's Patches of Mice.

Leon Ullrich,Anika Janssen,Koichi Ikuta,Anna-Lena Juergens,Immo Prinz,Abdi Demera,Anja Bubke,Joana Barros-Martins,Gwendolyn Elena Patzer,Inga Sandrock,Anneke Wilharm,Francesca Rampoldi,Yvonne Lueder

doi:10.3389/fimmu.2021.729607

Abstract

The mucosal immune system is the first line of defense against pathogens. Germinal centers (GCs) in the Peyer’s patches (PPs) of the small intestine are constantly generated through stimulation of the microbiota. In this study, we investigated the role of γδ T cells in the GC reactions in PPs. Most γδ T cells in PPs localized in the GCs and expressed a TCR composed of Vγ1 and Vδ6 chains. By using mice with partial and total γδ T cell deficiencies, we found that Vγ1+/Vδ6+ T cells can produce high amounts of IL-4, which drives the proliferation of GC B cells as well as the switch of GC B cells towards IgA. Therefore, we conclude that γδ T cells play a role in sustaining gut homeostasis and symbiosis via supporting the GC reactions in PPs.

Highlights

Mucosal surfaces of the body are a major entry site for non-self-antigens
As most of the gd T cells in Peyer’s patches (PPs) are located within the germinal centers (GCs), we examined the influence of gd T cell on GC B cells
As IgA+ GC B cells were reduced in absence of gd T cells, we investigated the concentration of IgA in the feces of Tcrd−/−, Vg1−/−, Vg4−/−/Vg6−/−, depleted, and non-depleted Tcrd-GDL mice

Summary

INTRODUCTION

Mucosal surfaces of the body are a major entry site for non-self-antigens. The gut-associated lymphoid tissue (GALT) represents the major challenging site for the mucosal immune system, as it has to protect against harmful pathogens, preserve tissue integrity, but should maintain the tolerance towards commensal microbiota and food antigens [1, 2]. Selected GC B cells can recirculate to the DZ to perform multiple rounds of SHM and selection for high-affinity binding to gd T Cells in Peyer’s Patches the antigen [22, 23]. These movements between LZ and DZ are regulated by mutual up- and downregulation of CXCR4 and CD86 expression on the surface of the GC B cells [24]. We found that a restricted subset of Vg1+ T cells in PPs expressing the Vd6 chain produced IL-4, influencing B cell isotype switch towards IgA

MATERIAL AND METHODS

RESULTS

B Cells During Salmonella Infection

DISCUSSION

ETHICS STATEMENT