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

• Published in: Nature communications Vol. 8; no. 1; pp. 1591 - 11
• Main Authors: Cruz-Adalia, Aránzazu, Ramirez-Santiago, Guillermo, Osuna-Pérez, Jesús, Torres-Torresano, Mónica, Zorita, Virgina, Martínez-Riaño, Ana, Boccasavia, Viola, Borroto, Aldo, Martínez del Hoyo, Gloria, González-Granado, José María, Alarcón, Balbino, Sánchez-Madrid, Francisco, Veiga, Esteban
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.11.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/1619/554/1898; 631/250/251; Animals; Antigen Presentation - immunology; Antigen-presenting cells; Antigens; Antigens, Bacterial - immunology; Bacteria; Cancer; Cancer immunotherapy; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Cross-Priming - immunology; Cytotoxicity; Cytotoxicity, Immunologic - immunology; Dendritic cells; Humanities and Social Sciences; Immune response; Immunologic Memory - immunology; Immunological memory; Immunological Synapses - immunology; Immunotherapy; Lymphocytes; Lymphocytes T; Memory cells; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; PD-1 protein; Phagocytosis; Phagocytosis - immunology; Priming; Programmed Cell Death 1 Receptor - immunology; Science; Science (multidisciplinary); T cell receptors; Tumors
• DOI: 10.1038/s41467-017-01661-7
• ISSN: 2041-1723

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. Antigen presentation is generally considered the domain of innate immune cells, but CD4 + T cells can transphagocytose bacteria from infected dendritic cells. Here the authors show CD4 + T cells can transphagocytose bacterial and tumour antigens and present them to CD8 + T cells to activate memory and cytotoxic functions.