Tissue-Resident Macrophages Limit Pulmonary CD8 Resident Memory T Cell Establishment

• Published in: Frontiers in immunology 2019-10, Vol.10, p.2332-2332
• Main Authors: Goplen, Nick P, Huang, Su, Zhu, Bibo, Cheon, In Su, Son, Young Min, Wang, Zheng, Li, Chaofan, Dai, Qigang, Jiang, Li, Sun, Jie
• Format: Article
• Language: English
• Subjects: alveolar macrophage; CD69; CD8 T cell differentiation; Immunology; influenza; PPAR-γ; tissue-resident memory
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.02332

Tissue resident memory CD8 T cells (T ) serve as potent local sentinels and contribute significantly to protective immunity against intracellular mucosal pathogens. While the molecular and transcriptional underpinnings of T differentiation are emerging, how T establishment is regulated by other leukocytes is largely unclear. Here, we observed that expression of PPAR-γ in the myeloid compartment was a negative regulator of CD8 T establishment following influenza virus infection. Interestingly, myeloid deficiency of PPAR-γ resulted in selective impairment of the tissue-resident alveolar macrophage (AM) compartment during primary influenza infection, suggesting that AM are likely negative regulators of CD8 T differentiation. Indeed, influenza-specific CD8 T cell numbers were increased following early, but not late ablation of AM using the CD169-DTR model. Importantly, these findings were specific to the parenchyma of infected tissue as circulating memory T cell frequencies in lung and T and T in spleen were largely unaltered following macrophage ablation. Further, the magnitude of the effector response could not explain these observations. These data indicate local regulation of pulmonary T differentiation is alveolar macrophage dependent. These, findings could aid in vaccine design aimed at increasing T density to enhance protective immunity, or deflating their numbers in conditions where they cause overt or veiled chronic pathologies.