title: Opa+ and Opa- isolates of Neisseria meningitidis and Neisseria gonorrhoeae induce sustained proliferative responses in human CD4+ T cells.
abstract: T cells may interact with a number of bacterial surface antigens, an encounter which has the potential to downmodulate host immune responses. Neisseria meningitidis, a human colonizer and an agent of septicemia and meningitis, expresses Opa proteins which interact with the CEACAM1 receptor expressed on activated T cells. Since CEACAM1 can act as an inhibitory receptor and T cells in subepithelial tissues may encounter whole bacteria, which often express Opa proteins in vivo, this study assessed primarily if Opa proteins expressed on meningococci affect T-cell functions. In addition, Opa-containing outer membrane vesicles (OMV) have been used as vaccine antigens, and therefore Opa+ and Opa- OMV were also studied. While Opa+ bacteria adhered to CEACAM-expressing T cells, both the Opa+ and Opa- phenotypes induced no to a small transient depression, followed by a prolonged increase in proliferation as well as cytokine production. Such responses were also observed with heat-killed bacteria or OMV. In addition, while anti-CEACAM antibodies alone inhibited proliferation, on coincubation of T cells with bacteria and the antibodies, bacterial effects predominated and were Opa independent. Thus, while Opa proteins of N. meningitidis can bind to T-cell-expressed CEACAM1, this is not sufficient to overcome the T-cell recognition of bacterial factors, which results in a proliferative and cytokine response, an observation consistent with the ability of the host to establish lasting immunity to Opa-expressing meningococci that it frequently encounters. The data also imply that Opa-proficient vaccine preparations may not necessarily inhibit T-cell functions via CEACAM1 binding.
authors.affiliation: Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Abdel-Rahman
authors.initials: AR
authors.lastname: Youssef
authors.forename: Michiel
authors.initials: M
authors.lastname: van der Flier
authors.forename: Silvia
authors.initials: S
authors.lastname: Estevão
authors.forename: Nico G
authors.initials: NG
authors.lastname: Hartwig
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.forename: Mumtaz
authors.initials: M
authors.lastname: Virji
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008589:Meningococcal Infections / Q000276:immunology* / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000276:immunology* / Q000378:metabolism; D009345:Neisseria meningitidis / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype
chemical_list: D000942:Antigens, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C090348:Opa protein, Neisseria