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 bacteria. The immunopathogenesis of this tissue response to infection has not been fully elucidated. Previous studies have suggested that T cells are involved in the pathologic process, but the role of these cells remains unclear. To delineate the mechanism by which T cells mediate abscess formation associated with intra-abdominal sepsis, the role of T-cell activation and the contribution of antigen-presenting cells via CD28-B7 costimulation were investigated. T cells activated in vitro by zwitterionic bacterial polysaccharides (Zps) known to induce abscess formation required CD28-B7 costimulation and, when adoptively transferred to the peritoneal cavity of naïve rats, promoted abscess formation. Blockade of T-cell activation via the CD28-B7 pathway in animals with CTLA4Ig prevented abscess formation following challenge with different bacterial pathogens, including Staphylococcus aureus, Bacteroides fragilis, and a combination of Enterococcus faecium and Bacteroides distasonis. In contrast, these animals had an increased abscess rate following in vivo T-cell activation via CD28 signaling. Abscess formation in vivo 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 activation via the CD28-B7-2 pathway.
Tzianabos
A O
AO
Channing Laboratory, Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. atzianabos@channing.harvard.edu
Chandraker
A
A
Kalka-Moll
W
W
Stingele
F
F
Dong
V M
VM
Finberg
R W
RW
Peach
R
R
Sayegh
M H
MH
D000069594:Abatacept; D000038:Abscess / Q000209:etiology*; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000494:pharmacology; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D006801:Humans; D018796:Immunoconjugates; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497966:Cd86 protein, rat; C556708:Ctla4 protein, rat; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D000069594:Abatacept