Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8+ T cells

• Published in: Nature communications 2015-05, Vol.6 (1), p.7089, Article 7089
• Main Authors: Martinet, Valérie, Tonon, Sandrine, Torres, David, Azouz, Abdulkader, Nguyen, Muriel, Kohler, Arnaud, Flamand, Véronique, Mao, Chai-An, Klein, William H., Leo, Oberdan, Goriely, Stanislas
• Format: Article
• Language: English
• Subjects: 13/31; 38/1; 38/15; 631/250/127/1212; 631/250/2152/1566/1571; 631/80/86; 692/698/1543/1565/1597/554/1834; Animals; Antigens - metabolism; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - metabolism; Gene Expression Regulation - drug effects; Homeostasis - drug effects; Humanities and Social Sciences; Immunity, Innate - drug effects; Immunologic Memory - drug effects; Immunologic Memory - genetics; Interferon Type I - metabolism; Interferon-gamma - biosynthesis; Interferon-Stimulated Gene Factor 3, gamma Subunit - metabolism; Mice, Inbred BALB C; Mice, Inbred C57BL; multidisciplinary; Poly I-C - pharmacology; Receptor, Interferon alpha-beta - deficiency; Receptor, Interferon alpha-beta - metabolism; Science; Science (multidisciplinary); Signal Transduction - drug effects; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; Thymocytes - drug effects; Thymocytes - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms8089

CD8 + T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for the development of these unconventional memory cells. Herein, we show that type I interferon signalling in CD8 + T cells directly activates Eomes gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of ‘virtual memory’ CD8 + T cells are strongly affected in absence of type I interferon signalling. In addition, type I interferons induce a sustained expansion of ‘virtual memory’ CD8 + T cells in an Eomes-dependent fashion. We further show that the development of ‘innate thymic’ CD8 + T cells is dependent on the same pathway. In conclusion, we demonstrate that type I interferon signalling in CD8 + T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8 + T cells. Eomesodermin is the key transcription factor for the development of ‘virtual memory’ T cells that develop in the absence of antigen-driven activation. Here the authors show that type I interferons directly activate eomesodermin and contribute to the homeostasis of virtual memory CD8 + T cells.