Development of Th1-type immune responses requires the type I cytokine receptor TCCR

• Published in: Nature (London) Vol. 407; no. 6806; pp. 916 - 920
• Main Authors: Chen, Q, Ghilardi, N, Wang, H, Baker, T, Xie, M H, Gurney, A, Grewal, I S, de Sauvage, F J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 19.10.2000
• Subjects: Amino Acid Sequence; Animals; Cancer; CD4-Positive T-Lymphocytes - immunology; Cell differentiation; Cells; Cells, Cultured; Cellular biology; Cytokines; Female; Gene Targeting; Hemocyanins - immunology; Humans; Immune response; Immune system; Immunoglobulin Isotypes - immunology; Interferon-gamma - biosynthesis; Leukopoiesis - physiology; Listeria monocytogenes; Listeria monocytogenes - immunology; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Receptors, Cytokine - genetics; Receptors, Cytokine - immunology; Receptors, Cytokine - isolation & purification; Receptors, Cytokine - metabolism; Sequence Homology, Amino Acid; TCCR protein; Th1 Cells - cytology; Th1 Cells - immunology; Tissue Distribution
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35038103

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.