The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses.
We investigated the in vivo function of the B7 family member B7-H3 (also known as B7RP-2) by gene targeting. B7-H3 inhibited T cell proliferation mediated by antibody to T cell receptor or allogeneic antigen-presenting cells. B7-H3-deficient mice developed more severe airway inflammation than did wild-type mice in conditions in which T helper cells differentiated toward type 1 (T(H)1) rather than type 2 (T(H)2). B7-H3 expression was consistently enhanced by interferon-gamma but suppressed by interleukin 4 in dendritic cells. B7-H3-deficient mice developed experimental autoimmune encephalomyelitis several days earlier than their wild-type littermates, and accumulated higher concentrations of autoantibodies to DNA. Thus, B7-H3 is a negative regulator that preferentially affects T(H)1 responses.
Suh
Woong-Kyung
WK
Advanced Medical Discovery Institute, Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada. wsuh@uhnres.utoronto.ca
Gajewska
Beata U
BU
Okada
Hitoshi
H
Gronski
Matthew A
MA
Bertram
Edward M
EM
Dawicki
Wojciech
W
Duncan
Gordon S
GS
Bukczynski
Jacob
J
Plyte
Suzanne
S
Elia
Andrew
A
Wakeham
Andrew
A
Itie
Annick
A
Chung
Stephen
S
Da Costa
Joan
J
Arya
Sudha
S
Horan
Tom
T
Campbell
Pauline
P
Gaida
Kevin
K
Ohashi
Pamela S
PS
Watts
Tania H
TH
Yoshinaga
Steven K
SK
Bray
Mark R
MR
Jordana
Manel
M
Mak
Tak W
TW
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D001323:Autoantibodies; D060887:B7 Antigens; D018122:B7-1 Antigen; C486038:Cd276 protein, mouse; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma