Blimp-1 Rather Than Hobit Drives the Formation of Tissue-Resident Memory CD8+ T Cells in the Lungs

Abstract

Tissue-resident memory CD8⁺ T (T_RM) cells that develop in the epithelia at portals of pathogen entry are important for improved protection against re-infection. CD8⁺ T_RM cells within the skin and the small intestine are long-lived and maintained independently of circulating memory CD8⁺ T cells. In contrast to CD8⁺ T_RM cells at these sites, CD8⁺ T_RM cells that arise after influenza virus infection within the lungs display high turnover and require constant recruitment from the circulating memory pool for long-term persistence. The distinct characteristics of CD8⁺ T_RM cell maintenance within the lungs may suggest a unique program of transcriptional regulation of influenza-specific CD8⁺ T_RM cells. We have previously demonstrated that the transcription factors Hobit and Blimp-1 are essential for the formation of CD8⁺ T_RM cells across several tissues, including skin, liver, kidneys, and the small intestine. Here, we addressed the roles of Hobit and Blimp-1 in CD8⁺ T_RM cell differentiation in the lungs after influenza infection using mice deficient for these transcription factors. Hobit was not required for the formation of influenza-specific CD8⁺ T_RM cells in the lungs. In contrast, Blimp-1 was essential for the differentiation of lung CD8⁺ T_RM cells and inhibited the differentiation of central memory CD8⁺ T (T_CM) cells. We conclude that Blimp-1 rather than Hobit mediates the formation of CD8⁺ T_RM cells in the lungs, potentially through control of the lineage choice between T_CM and T_RM cells during the differentiation of influenza-specific CD8⁺ T cells.

Keywords: T cell differentiation; TCF-1; blimp-1/PRDM1; central memory CD8(+) T cells; hobit; influenza virus infection; lung T cell; tissue-resident memory CD8(+) T cells.