Development of Th1-type immune responses requires the type I cytokine receptor TCCR.
On antigen challenge, T-helper cells differentiate into two functionally distinct subsets, Th1 and Th2, characterized by the different effector cytokines that they secrete. Th1 cells produce interleukin (IL)-2, interferon-gamma (IFN-gamma) and lymphotoxin-beta, which mediate pro-inflammatory functions critical for the development of cell-mediated immune responses, whereas Th2 cells secrete cytokines such as IL-4, IL-5 and IL-10 that enhance humoral immunity. This process of T-helper cell differentiation is tightly regulated by cytokines. Here we report a new member of the type I cytokine receptor family, designated T-cell cytokine receptor (TCCR). When challenged in vivo with protein antigen, TCCR-deficient mice had impaired Th1 response as measured by IFN-gamma production. TCCR-deficient mice also had increased susceptibility to infection with an intracellular pathogen, Listeria monocytogenes. In addition, levels of antigen-specific immunoglobulin-gamma2a, which are dependent on Th1 cells, were markedly reduced in these mice. Our results demonstrate the existence of a new cytokine receptor involved in regulating the adaptive immune response and critical to the generation of a Th1 response.
Chen
Q
Q
Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA.
Ghilardi
N
N
Wang
H
H
Baker
T
T
Xie
M H
MH
Gurney
A
A
Grewal
I S
IS
de Sauvage
F J
FJ
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D018390:Gene Targeting; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D019891:Leukopoiesis / Q000502:physiology; D008089:Listeria monocytogenes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D018123:Receptors, Interleukin; D017386:Sequence Homology, Amino Acid; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D014018:Tissue Distribution
C484747:Il27ra protein, mouse; D007132:Immunoglobulin Isotypes; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin