title: Role of ICOS versus CD28 in antiviral immunity.
abstract: The costimulatory protein ICOS is inducibly expressed on activated T cells. Previous results have shown that ICOS(-/-) mice are defective in germinal center formation, antibody (Ab) production and class switch as well as Th1 and Th2 cytokine production in response to protein or parasite antigens. However, ICOS-Ig failed to block antiviral Ab responses. To date the immune response to viruses has not been examined in ICOS(-/-) mice. In this report we compared antiviral Ab responses to LCMV, VSV and influenza virus in ICOS(-/-) versus wild-type mice. Our results show that ICOS is important in the Ab response to all three viruses, with greater effects on primary as compared to secondary responses. Although ICOS(-/-) mice are impaired in some immune responses following influenza infection, the effects were less severe than for CD28(-/-) mice. There was no defect in initial influenza-specific CD8 T cell expansion in ICOS(-/-) mice or in cytotoxic effector function. However, ICOS was important in maintaining CD4 cytokine production and CD8 T cell numbers late in the primary response. Upon secondary infection, ICOS(-/-) mice show wild-type levels of influenza-specific CD8 T cells, whereas CD28(-/-) mice show greatly impaired secondary CD8 T cell expansion. Overall, our results show that ICOS plays a clear role in the primary response to viruses at the level of Ab production, germinal center formation and Th cytokine production, but has diminished effects following secondary viral challenge.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Canada.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Bertram
authors.forename: Anna
authors.initials: A
authors.lastname: Tafuri
authors.forename: Arda
authors.initials: A
authors.lastname: Shahinian
authors.forename: Vera S F
authors.initials: VS
authors.lastname: Chan
authors.forename: Lukas
authors.initials: L
authors.lastname: Hunziker
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Tania H
authors.initials: TH
authors.lastname: Watts
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007134:Immunoglobulin Switch Region; D060889:Inducible T-Cell Co-Stimulator Protein; D007376:Interleukin-2 / Q000096:biosynthesis; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014780:Viruses / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; C556694:Icos protein, mouse; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D007376:Interleukin-2