title: Pathogen-induced inflammatory environment controls effector and memory CD8+ T cell differentiation.
abstract: In response to infection, CD8(+) T cells integrate multiple signals and undergo an exponential increase in cell numbers. Simultaneously, a dynamic differentiation process occurs, resulting in the formation of short-lived effector cells (SLECs; CD127(low)KLRG1(high)) and memory precursor effector cells (CD127(high)KLRG1(low)) from an early effector cell that is CD127(low)KLRG1(low) in phenotype. CD8(+) T cell differentiation during vesicular stomatitis virus infection differed significantly than during Listeria monocytogenes infection with a substantial reduction in early effector cell differentiation into SLECs. SLEC generation was dependent on Ebi3 expression. Furthermore, SLEC differentiation during vesicular stomatitis virus infection was enhanced by administration of CpG-DNA, through an IL-12-dependent mechanism. Moreover, CpG-DNA treatment enhanced effector CD8(+) T cell functionality and memory subset distribution, but in an IL-12-independent manner. Population dynamics were dramatically different during secondary CD8(+) T cell responses, with a much greater accumulation of SLECs and the appearance of a significant number of CD127(high)KLRG1(high) memory cells, both of which were intrinsic to the memory CD8(+) T cell. These subsets persisted for several months but were less effective in recall than memory precursor effector cells. Thus, our data shed light on how varying the context of T cell priming alters downstream effector and memory CD8(+) T cell differentiation.
authors: Center for Integrated Immunology and Vaccine Research, Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA. joshua.obar@montana.edu
authors: Joshua J
authors: JJ
authors: Obar
authors: Evan R
authors: ER
authors: Jellison
authors: Brian S
authors: BS
authors: Sheridan
authors: David A
authors: DA
authors: Blair
authors: Quynh-Mai
authors: QM
authors: Pham
authors: Julianne M
authors: JM
authors: Zickovich
authors: Leo
authors: L
authors: Lefrançois
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007156:Immunologic Memory; D007249:Inflammation / Q000382:microbiology / Q000821:virology; D008088:Listeriosis / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D054243:Vesicular Stomatitis / Q000276:immunology* / Q000473:pathology*
chemical_list: D010047:Ovalbumin