IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells.
An efficient Th1-driven adaptive immune response requires activation of the T cell receptor and secretion of the T cell stimulatory cytokine IL-12 by activated antigen-presenting cells. IL-12 triggers Th1 polarization of naive CD4(+) T cells and secretion of IFN-gamma. We describe a new heterodimeric cytokine termed IL-27 that consists of EBI3, an IL-12p40-related protein, and p28, a newly discovered IL-12p35-related polypeptide. IL-27 is an early product of activated antigen-presenting cells and drives rapid clonal expansion of naive but not memory CD4(+) T cells. It also strongly synergizes with IL-12 to trigger IFN-gamma production of naive CD4(+) T cells. IL-27 mediates its biologic effects through the orphan cytokine receptor WSX-1/TCCR.
DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA.
Stefan
S
Pflanz
Jackie C
JC
Timans
Jeanne
J
Cheung
Rency
R
Rosales
Holger
H
Kanzler
Jonathan
J
Gilbert
Linda
L
Hibbert
Tatyana
T
Churakova
Marilyn
M
Travis
Elena
E
Vaisberg
Wendy M
WM
Blumenschein
Jeanine D
JD
Mattson
Janet L
JL
Wagner
Wayne
W
To
Sandra
S
Zurawski
Terrill K
TK
McClanahan
Daniel M
DM
Gorman
J Fernando
JF
Bazan
Rene
R
de Waal Malefyt
Donna
D
Rennick
Robert A
RA
Kastelein
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002352:Carrier Proteins / Q000032:analysis*; D002455:Cell Division; D019281:Dimerization; D005982:Glutathione Transferase; D006023:Glycoproteins / Q000032:analysis*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D007378:Interleukins / Q000737:chemistry / Q000502:physiology*; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D011487:Protein Conformation; D018121:Receptors, Cytokine / Q000378:metabolism; D018123:Receptors, Interleukin; D016415:Sequence Alignment; D018417:Th1 Cells / Q000276:immunology*
D002352:Carrier Proteins; C097732:EBI3 protein, human; D006023:Glycoproteins; C117709:Gsto1 protein, mouse; C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D018664:Interleukin-12; D007371:Interferon-gamma; D005982:Glutathione Transferase