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Infection and Immunity, February 2006, p. 1050-1061, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1050-1061.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Role for Inducible Costimulator in Control of Salmonella enterica Serovar Typhimurium Infection in Mice

Mariana Vidric,¹ Anna Tafuri Bladt,^2, Umberto Dianzani,³ and Tania H. Watts^1*

Department of Immunology,¹ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5S 1A8,² Interdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Medical Sciences, "A. Avogadro" University of Eastern Piedmont at Novara, Novara, Italy³

Received 4 July 2005/ Returned for modification 8 August 2005/ Accepted 12 November 2005

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.

Editor: J. L. Flynn

Present address: Hopital Necker, INSERM U580, 161 rue de Sevres, 75015 Paris, France.

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