Bacterial pathogens induce abscess formation by CD4(+) T-cell activation via the CD28-B7-2 costimulatory pathway

Abscesses are a classic host response to infection by many pathogenic bacte ria. The immunopathogenesis of this tissue response to infection has not be en fully elucidated. Previous studies have suggested that T cells are invol ved in the pathologic process, but the role of these cells remains unclear. To delineate the mechanism by which T cells mediate abscess formation asso ciated with intra-abdominal sepsis, the role of T-cell activation and the c ontribution of antigen-presenting cells via CD28-B7 costimulation were inve stigated. T cells activated in vitro by zwitterionic bacterial polysacchari des (Zps) known to induce abscess formation required CD28-B7 costimulation and, when adoptively transferred to the peritoneal cavity of naive rats, pr omoted abscess formation. Blockade of T-cell activation via the CD28-B7 pat hway in animals with CTLA4Ig prevented abscess formation following challeng e with different bacterial pathogens, including Staphylococcus aureus, Bact eroides fragilis, and a combination of Enterococcus faecium and Bacteroides distasonis. In contrast, these animals had an increased abscess rate follo wing in vivo T-cell activation via CD28 signaling. Abscess formation in viv o and T-cell activation in vitro required costimulation by B7-2 but not B7- 1. These results demonstrate that abscess formation by pathogenic bacteria is under the control of a common effector mechanism that requires T-cell ac tivation via the CD28-B7-2 pathway.