ICOS is essential for effective T-helper-cell responses.
The outcome of T-cell responses after T-cell encounter with specific antigens is modulated by co-stimulatory signals, which are required for both lymphocyte activation and development of adaptive immunity. ICOS, an inducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in vivo genetic evidence that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B-cell responses. Germinal centre formation is impaired and immunoglobulin class switching, including production of allergy-mediating IgE, is defective. ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-gamma.
Tafuri
A
A
Amgen Institute, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.
Shahinian
A
A
Bladt
F
F
Yoshinaga
S K
SK
Jordana
M
M
Wakeham
A
A
Boucher
L M
LM
Bouchard
D
D
Chan
V S
VS
Duncan
G
G
Odermatt
B
B
Ho
A
A
Itie
A
A
Horan
T
T
Whoriskey
J S
JS
Pawson
T
T
Penninger
J M
JM
Ohashi
P S
PS
Mak
T W
TW
D000818:Animals; D000941:Antigens / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D002450:Cell Communication; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D005362:Ficoll / Q000031:analogs & derivatives* / Q000276:immunology; D005434:Flow Cytometry; D018390:Gene Targeting; D018858:Germinal Center / Q000502:physiology; D006433:Hemocyanins / Q000276:immunology; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology*; D014301:Trinitrobenzenes / Q000276:immunology
D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; C020529:TNP-ficoll; D014301:Trinitrobenzenes; D015847:Interleukin-4; D005362:Ficoll; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin