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Usage and Promote Anergy, Resulting in Protection against Experimental Abscess Formation1
,¶
* Nestlé Research Center, Vers-chez-les-Blanc, Lausanne, Switzerland;
Division of Immunology and Allergology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461;
Channing Laboratory, Brigham and Woman’s Hospital, Harvard Medical School, Boston, MA 02115; and
¶ Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115
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. V
repertoire analysis using RT-PCR demonstrates that Zps have broad V 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.
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