Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses

Aránzazu Cruz-Adalia,Francisco Sánchez-Madrid,Esteban Veiga,Gloria Martínez Del Hoyo,Mónica Torres-Torresano,Ana Martínez-Riaño,Virgina Zorita,Guillermo Ramirez-Santiago,Viola Boccasavia,Balbino Alarcón,Aldo Borroto,Jesús Osuna-Pérez,José María González-Granado

doi:10.1038/s41467-017-01661-7

Abstract

Bacterial phagocytosis and antigen cross-presentation to activate CD8+ T cells are principal functions of professional antigen presenting cells. However, conventional CD4+ T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8+ T cells, which proliferate and become cytotoxic in response. CD4+ T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8+ T cells with low PD-1 expression. Moreover, transphagocytic CD4+ T cells induce protective anti-tumour immune responses by priming CD8+ T cells, highlighting the potential of CD4+ T cells as a tool for cancer immunotherapy.

Highlights

Bacterial phagocytosis and antigen cross-presentation to activate CD8+ T cells are principal functions of professional antigen presenting cells
OT-II transgenic mouse were co-cultured with bone marrowderived dendritic cells (DC) (BM-DC) infected with L. monocytogenes expressing ovoalbumin (Listeria-OVA)[23] or with its isogenic wild type strain (Listeria-WT) and decorated with OVAp-II antigen
Infected DC-T-cell conjugates were allowed to form (24 h), after which CD4+ T cells were repurified by cell sorting (Supplementary Fig. 1A). tpCD4+ T cells that captured L. monocytogenes after 2 h conjugate formation are shown in Supplementary Fig. 1B; quantification of bacteria capture/destruction was reported[19]

Summary

Introduction

Bacterial phagocytosis and antigen cross-presentation to activate CD8+ T cells are principal functions of professional antigen presenting cells. We show that transphagocytic T cells present bacterial antigens to naive CD8+ T cells, which proliferate and become cytotoxic in response. T he immune response to intracellular bacterial pathogens (such as Listeria monocytogenes) and cancer are similar in many ways, and require the participation of CD8+ effector. As almost all cells express MHC-I, malignant cells (expressing neo-antigens) or infected cells (expressing pathogen antigens) can be eliminated by effector CD8+ T cells. To eliminate these types of cells directly, antigen-specific CD8+ T cells must first be activated (or ‘primed’) by professional APCs3. APC presentation of exogenous antigens, such as bacterial antigens, via MHC-I is termed cross-presentation[3,4], and is crucial for CD8+

Methods

Results

Conclusion