Keith D Kauffman, Shunsuke Sakai, Nickiana E Lora, Sivaranjani Namasivayam, Paul J Baker, Olena Kamenyeva, Taylor W Foreman, Christine E Nelson, Deivide Oliveira-de-Souza, Caian L Vinhaes, Ziv Yaniv, Cecilia S Lindestam Arleham, Alessandro Sette, Gordon J Freeman, Rashida Moore, Alan Sher, Katrin D Mayer-Barber, Bruno B Andrade, Juraj Kabat, Laura E Via, Daniel L Barber
Boosting immune cell function by targeting the coinhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here, we examine the role of PD-1 during Mycobacterium tuberculosis (Mtb) infection of rhesus macaques. Animals treated with anti-PD-1 monoclonal antibody developed worse disease and higher granuloma bacterial loads compared with isotype control-treated monkeys. PD-1 blockade increased the number and functionality of granuloma Mtb-specific CD8 T cells. In contrast, Mtb-specific CD4 T cells in anti-PD-1-treated macaques were not increased in number or function in granulomas, expressed increased levels of CTLA-4, and exhibited reduced intralesional trafficking in live imaging studies...
January 15, 2021: Science Immunology