title: IL-10 Regulates Memory T Cell Development and the Balance between Th1 and Follicular Th Cell Responses during an Acute Viral Infection.
abstract: T cells provide protective immunity against infections by differentiating into effector cells that contribute to rapid pathogen control and by forming memory populations that survive over time and confer long-term protection. Thus, understanding the factors that regulate the development of effective T cell responses is beneficial for the design of vaccines and immune-based therapies against infectious diseases. Cytokines play important roles in shaping T cell responses, and IL-10 has been shown to modulate the differentiation of CD4 and CD8 T cells. In this study, we report that IL-10 functions in a cell-extrinsic manner early following acute lymphocytic choriomeningitis virus infection to suppress the magnitude of effector Th1 responses as well as the generation of memory CD4 and CD8 T cells. We further demonstrate that the blockade of IL-10 signaling during the priming phase refines the functional quality of memory CD4 and CD8 T cells. This inhibition strategy resulted in a lower frequency of virus-specific follicular Th (Tfh) cells and increased the Th1 to Tfh ratio. Nevertheless, neither germinal center B cells nor lymphocytic choriomeningitis virus-specific Ab levels were influenced by the blockade. Thus, our studies show that IL-10 influences the balance between Th1 and Tfh cell differentiation and negatively regulates the development of functionally mature memory T cells.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294; and.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Mollo
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Harrington
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294; and azajac@uab.edu.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Zajac
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10