title: Differentiation of distinct long-lived memory CD4 T cells in intestinal tissues after oral Listeria monocytogenes infection.
abstract: Mucosal antigen-specific CD4 T-cell responses to intestinal pathogens remain incompletely understood. Here we examined the CD4 T-cell response after oral infection with an internalin A 'murinized' Listeria monocytogenes (Lm). Oral Lm infection induced a robust endogenous listeriolysin O (LLO)-specific CD4 T-cell response with distinct phenotypic and functional characteristics in the intestine. Circulating LLO-specific CD4 T cells transiently expressed the 'gut-homing' integrin α4β7and accumulated in the intestinal lamina propria and epithelium where they were maintained independent of interleukin (IL)-15. The majority of intestinal LLO-specific CD4 T cells were CD27-Ly6C-and CD69+CD103-while the lymphoid LLO-specific CD4 T cells were heterogeneous based on CD27 and Ly6C expression and predominately CD69-. LLO-specific effector CD4 T cells transitioned into a long-lived memory population that phenotypically resembled their parent effectors and displayed hallmarks of residency. In addition, intestinal effector and memory CD4 T cells showed a predominant polyfunctional Th1 profile producing IFNγ, TNFα, and IL-2 at high levels with minimal but detectable levels of IL-17A. Depletion of CD4 T cells in immunized mice led to elevated bacterial burden after challenge infection highlighting a critical role for memory CD4 T cells in controlling intestinal intracellular pathogens.
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Romagnoli
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Fu
authors.affiliation: Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA.
authors.forename: C
authors.initials: C
authors.lastname: Khairallah
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: Q M
authors.initials: QM
authors.lastname: Pham
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: L
authors.initials: L
authors.lastname: Puddington
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Khanna
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: L
authors.initials: L
authors.lastname: Lefrançois
authors.affiliation: Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Sheridan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000276:immunology; D006460:Hemolysin Proteins / Q000276:immunology; D007156:Immunologic Memory; D039441:Integrin alpha4 / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D016207:Cytokines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D039641:Integrin beta Chains; D016201:Receptors, Lymphocyte Homing; C091368:integrin beta7; C069761:internalin protein, Bacteria; D039441:Integrin alpha4; C038705:hlyA protein, Listeria monocytogenes