title: Zwitterionic polysaccharides stimulate T cells with no preferential V beta usage and promote anergy, resulting in protection against experimental abscess formation.
abstract: Zwitterionic polysaccharides (Zps) from pathogenic bacteria, such as Bacteroides fragilis, are virulence factors responsible for abscess formation associated with intra-abdominal sepsis. The underlying cellular mechanism for abscess formation requires T cell activation. Conversely, abscess formation can be prevented by prophylactic s.c. injection of purified Zps alone, a process also dependent on T cells. Hence, the modulatory role of T cells in abscess formation was investigated. We show that Zps interact directly with T cells with fast association/dissociation kinetics. Vbeta repertoire analysis using RT-PCR demonstrates that Zps have broad Vbeta usage. Zps-specific hybridomas responded to a variety of other Zps, but not to a nonzwitterionic polysaccharide, indicating cross-reactivity between different Zps. Furthermore, Zps-reactive T cell hybridomas could effectively transfer protection against abscess formation. Analysis of the proliferative capacity of T cells recovered from Zps-treated animals revealed that these T cells are anergic to subsequent stimulation by the different Zps or to alloantigens in an MLR. This anergic response was relieved by addition of IL-2. Taken together, the data show that this class of polysaccharides interacts directly with T cells in a nonbiased manner to elicit an IL-2-dependent anergic response that confers protection against abscess formation.
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, Lausanne, Switzerland. francesca.stingele@bluewin.ch
authors.forename: Francesca
authors.initials: F
authors.lastname: Stingele
authors.forename: Blaise
authors.initials: B
authors.lastname: Corthésy
authors.forename: Nicole
authors.initials: N
authors.lastname: Kusy
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Kasper
authors.forename: Arthur O
authors.initials: AO
authors.lastname: Tzianabos
mesh_terms: D000038:Abscess / Q000276:immunology* / Q000517:prevention & control*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001442:Bacteroides Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D001441:Bacteroides fragilis / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D017635:Clonal Anergy / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D006825:Hybridomas; D007477:Ions; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew / Q000382:microbiology; D017208:Rats, Wistar; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D007477:Ions; D010455:Peptides; D011135:Polysaccharides, Bacterial; D016693:Receptors, Antigen, T-Cell, alpha-beta