title: Evidence for naturally acquired T cell-mediated mucosal immunity to Neisseria meningitidis.
abstract: Naturally acquired protective immunity against Neisseria meningitidis is thought to partially explain the disparity between the high levels of carriage in the human nasopharynx and the rare incidence of disease. To investigate this immunity to Neisseria meningitidis at the mucosal level, in vitro cellular responses to outer membrane vesicle preparations derived from this pathogen were examined using mononuclear cells from the palatine tonsils of adults and children. Characterization of these responses was achieved by depletion of CD45RA(+), CD45RO(+), and CD19(+) populations and outer membrane vesicles derived from isogenic mutants expressing different serosubtypes of the major outer membrane protein, porin A (PorA), no PorA and membrane preparations from a mutant with no LPS (LpxA(-)). The magnitude of cellular proliferative responses against the outer membrane vesicles were strongly associated with age and were largely T cell mediated, involving both CD45RO(+) and CD45RA(+) T cell phenotypes. Responses were not dependent on LPS but consisted of both PorA cross-specific and non-PorA-dependent responses. Cellular immunity against Neisseria meningitidis was found to be frequently associated with systemic IgG Abs but was not associated with serum bactericidal Abs. For the first time our results demonstrate an age-associated acquisition of mucosal T effector/memory cell responses to Neisseria meningitidis. This mucosal cellular immunity can be present in the absence of serum bactericidal Abs, a classical marker of protective immunity.
authors.affiliation: Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol, United Kingdom. c.victoria.davenport@bristol.ac.uk
authors.forename: Victoria
authors.initials: V
authors.lastname: Davenport
authors.forename: Terry
authors.initials: T
authors.lastname: Guthrie
authors.forename: Jamie
authors.initials: J
authors.lastname: Findlow
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Neil A
authors.initials: NA
authors.lastname: Williams
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000276:immunology; D000907:Antibodies, Bacterial / Q000097:blood; D000940:Antigenic Variation / Q000502:physiology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology* / Q000382:microbiology; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D018272:Porins / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D018272:Porins; C057699:porin protein, Neisseria; D017493:Leukocyte Common Antigens