Role for inducible costimulator in control of Salmonella enterica serovar Typhimurium infection in mice.
Inducible costimulator (ICOS) is expressed on activated T cells and plays a key role in sustaining and enhancing the effector function of CD4 T cells. Given the function of this molecule in sustaining T-cell responses, we reasoned that ICOS might play an important role in a prolonged infection model, such as Salmonella infection of mice. To test this hypothesis, wild-type (WT) and ICOS-deficient (ICOS-/-) mice were infected systemically with a Salmonella enterica serovar Typhimurium strain expressing the chicken ovalbumin gene (Salmonella-OVA). ICOS-/- mice exhibited greater splenomegaly than WT mice and showed delayed bacterial clearance. The acquired immune response in this model was slow to develop. Maximal T-cell responses to Salmonella-OVA were detected at 3 weeks postinfection in both WT and ICOS-/- mice. CD4 T-cell-dependent gamma interferon production and a class switch to immunoglobulin G2a were severely reduced in ICOS-/- mice. ICOS-/- mice also exhibited a substantial defect in antigen-specific CD8 T-cell responses. In vitro, the effect of anti-ICOS on CD8 T-cell division was greater when CD8 T cells rather than CD4 T cells expressed ICOS, suggesting that the in vivo effects of ICOS on CD8 T cells could be direct. Taken together, these studies show that ICOS plays a critical role in control of Salmonella infection in mice, with effects on antibody, Th1, and CD8 T-cell responses.
Vidric
Mariana
M
Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
Bladt
Anna Tafuri
AT
Dianzani
Umberto
U
Watts
Tania H
TH
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D013163:Splenomegaly; D018417:Th1 Cells / Q000276:immunology*
D000907:Antibodies, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D010047:Ovalbumin