title: Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10-Mediated Responses.
abstract: Concurrent helminth infection potently inhibits T cell immunity; however, whether helminthes prevent T cell priming or skew clonal recruitment and effector differentiation is not known. Using coinfection with two natural mouse pathogens, Heligmosomoides polygyrus and Toxoplasma gondii, to investigate the negative impact of helminthes on the CD8 T cell response, we demonstrate helminth-induced suppression of IL-12-dependent differentiation of killer-like receptor G1+effector CD8 T cells and IFN-γ production. Nevertheless, reversal of helminth suppression of the innate IL-12 response of CD8α+dendritic cells, which occurred in STAT6-deficient mice, was not sufficient to normalize CD8 T cell differentiation. Instead, a combined deficiency in IL-4 and IL-10 was required to reverse the negative effects of helminth coinfection on the CD8 T cell response. Monoclonal T. gondii-specific CD8 T cells adoptively transferred into coinfected mice recapitulated the spectrum of helminth-induced effects on the polyclonal CD8 T response, indicating the lack of requirement for clonal skewing.
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101.|Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07101; and.
authors.forename: Andrew
authors.identifier: 0000-0002-6724-8399
authors.initials: A
authors.lastname: Marple
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101.|Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07101; and.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101.|Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07101; and.
authors.forename: Suhagi
authors.identifier: 0000-0003-3352-7274
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101.|Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07101; and.
authors.forename: Yanlin
authors.identifier: 0000-0002-0278-7543
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: High Performance and Research Computing Group, Office of Information Technology, Rutgers New Jersey Medical School, Rutgers University, Newark, NJ 07101.
authors.forename: Peicheng
authors.identifier: 0000-0003-4367-0875
authors.initials: P
authors.lastname: Du
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101.|Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07101; and.
authors.forename: William C
authors.initials: WC
authors.lastname: Gause
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101; yapgs@njms.rutgers.edu.|Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07101; and.
authors.forename: George S
authors.initials: GS
authors.lastname: Yap
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D060085:Coinfection / Q000276:immunology*; D004195:Disease Models, Animal; D006373:Helminthiasis / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology
chemical_list: D016753:Interleukin-10