title: Impact of inducible co-stimulatory molecule (ICOS) on T-cell responses and protection against Mycobacterium tuberculosis infection.
abstract: Even though Mycobacterium tuberculosis (Mtb) remains one of the top microbial killers, more than 90% of the 2 billion infected individuals never develop active tuberculosis (TB), indicating efficient immune control of infection in these individuals. Immune mechanisms promoting either control or reactivation of TB are incompletely understood. Kinetic analyses of T-cell responses against Mtb in C57BL/6 mice revealed surface expression of inducible co-stimulatory molecule (ICOS) on >30% of all CD4(+) T cells, suggesting a pivotal role of this costimulatory molecule of the CD28 family in TB control. Surprisingly, Mtb-infected ICOS(-/-) mice showed lower bacterial burden during the late chronic stage of infection as compared to WT controls. ICOS deficiency resulted in a reduced Mtb-specific CD8(+) T-cell response during late-stage infection. In contrast, the polyclonal CD4(+) Th1 response against Mtb was increased, most likely caused by diminished numbers and frequencies of Tregs. Thus, by altering effector T-cell populations differentially, ICOS signaling modulates TB control in the late stage of infection.
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Nouailles
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Day
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuhlmann
authors.forename: Delia
authors.initials: D
authors.lastname: Loewe
authors.forename: Anca
authors.initials: A
authors.lastname: Dorhoi
authors.forename: Pia
authors.initials: P
authors.lastname: Gamradt
authors.forename: Robert
authors.initials: R
authors.lastname: Hurwitz
authors.forename: Sabine
authors.initials: S
authors.lastname: Jörg
authors.forename: Lydia
authors.initials: L
authors.lastname: Pradl
authors.forename: Andreas
authors.initials: A
authors.lastname: Hutloff
authors.forename: Markus
authors.initials: M
authors.lastname: Koch
authors.forename: Mischo
authors.initials: M
authors.lastname: Kursar
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D007156:Immunologic Memory; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D015398:Signal Transduction; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein