Journal ArticleDOI
ICOS co-stimulatory receptor is essential for T-cell activation and function.
Chen Dong,Amy E. Juedes,Ulla Angela Temann,Ulla Angela Temann,Sujan Shresta,James P. Allison,Nancy H. Ruddle,Richard A. Flavell,Richard A. Flavell +8 more
Reads0
Chats0
TLDR
It is shown that T-cell activation and proliferation are defective in the absence of ICOS, and ICOS-/- mice showed greatly enhanced susceptibility to experimental autoimmune encephalomyelitis, indicating that ICOS has a protective role in inflammatory autoimmune diseases.Abstract:
T-lymphocyte activation and immune function are regulated by co-stimulatory molecules. CD28, a receptor for B7 gene products, has a chief role in initiating T-cell immune responses1,2. CTLA4, which binds B7 with a higher affinity, is induced after T-cell activation and is involved in downregulating T-cell responses3,4. The inducible co-stimulatory molecule (ICOS), a third member of the CD28/CTLA4 family, is expressed on activated T cells5,6. Its ligand B7H/B7RP-1 is expressed on B cells and in non-immune tissues after injection of lipopolysaccharide into animals6,7. To understand the role of ICOS in T-cell activation and function, we generated and analysed ICOS-deficient mice. Here we show that T-cell activation and proliferation are defective in the absence of ICOS. In addition, ICOS-/- T cells fail to produce interleukin-4 when differentiated in vitro or when primed in vivo. ICOS is required for humoral immune responses after immunization with several antigens. ICOS-/- mice showed greatly enhanced susceptibility to experimental autoimmune encephalomyelitis, indicating that ICOS has a protective role in inflammatory autoimmune diseases.read more
Citations
More filters
Journal ArticleDOI
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Heon Park,Zhaoxia Li,Xuexian O. Yang,Seon Hee Chang,Roza Nurieva,Yi Hong Wang,Ying Wang,Leroy Hood,Zhou Zhu,Qiang Tian,Chen Dong +10 more
TL;DR: In vivo, antibody to IL- 17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused Chemokine production and leukocyte infiltration, indicating a unique T helper lineage that regulates tissue inflammation.
Journal ArticleDOI
The b7 family revisited
TL;DR: The roles of the B7:CD28 family members in regulating immune responses are revisited, and the therapeutic potential of these families is discussed.
Journal ArticleDOI
The B7–CD28 superfamily
TL;DR: The current understanding of the new members of the B7 and CD28 families is summarized, their therapeutic potential is discussed, and other immunoregulatory pathways remain to be described.
Journal ArticleDOI
T Helper 17 Lineage Differentiation Is Programmed by Orphan Nuclear Receptors RORα and RORγ
Xuexian O. Yang,Bhanu P. Pappu,Roza Nurieva,Askar M. Akimzhanov,Hong Soon Kang,Yeonseok Chung,Li Ma,Bhavin Shah,Athanasia D. Panopoulos,Kimberly S. Schluns,Stephanie S. Watowich,Qiang Tian,Anton M. Jetten,Chen Dong +13 more
TL;DR: Th17 differentiation is directed by two lineage-specific nuclear receptors, ROR alpha and ROR gamma, and is induced by transforming growth factor-beta and interleukin-6 (IL-6), which is dependent on signal transducer and activator of transcription 3.
Journal ArticleDOI
B7-Dc, a New Dendritic Cell Molecule with Potent Costimulatory Properties for T Cells
Su Yi Tseng,Mizuto Otsuji,Kevin S. Gorski,Xin Huang,Jill E. Slansky,Sara I. Pai,Ahmed Shalabi,Tahiro Shin,Drew M. Pardoll,Haruo Tsuchiya +9 more
TL;DR: A new B7 family member, B7-DC, whose expression is highly restricted to DCs, was identified among a library of genes differentially expressed between DCs and activated macrophages, which may account for some of the unique activity of DC's, such as their ability to initiate potent T helper cell type 1 responses.
References
More filters
Journal ArticleDOI
Cd28/b7 system of t cell costimulation
TL;DR: This review summarizes the state of CD28/B7 immunobiology both in vitro and in vivo; summarizes the many experiments that have led to the current understanding of the participants in this complex receptor/ligand system; and illustrates the current models for CD28-mediated T cell and B cell regulation.
Journal ArticleDOI
ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28
Andreas Hutloff,Anna M. Dittrich,Katja C. Beier,Barbara Eljaschewitsch,Regine Kraft,Ionnis Anagnostopoulos,Richard A. Kroczek +6 more
TL;DR: The identification of a third member of this family of molecules, inducible co-stimulator (ICOS), which is a homodimeric protein of relative molecular mass 55,000–60,000 (Mr 55K–60K) indicates that ICOS is another major regulator of the adaptive immune system.
Journal ArticleDOI
T-cell co-stimulation through B7RP-1 and ICOS
Steven Kiyoshi Yoshinaga,John Whoriskey,Sanjay D. Khare,Ulla Sarmiento,Jane Guo,Tom Horan,Grace Shih,Ming Zhang,Marco A. Coccia,Tadahiko Kohno,Anna Tafuri-Bladt,David W. Brankow,Pauline Campbell,David Chang,Laura Chiu,Tianang Dai,Gordon S. Duncan,Gary Elliott,Ariela Hui,Susan McCabe,Sheila Scully,Arda Shahinian,Christine L. Shaklee,Gwyneth Van,Tak W. Mak,Giorgio Senaldi +25 more
TL;DR: A new murine co-stimulatory receptor–ligand pair is described that is structurally related to CD28–B7 and is involved in the adaptive immune response and defined as B7RP-1, which exhibits co- Stimulation activities in vitro and in vivo.
Journal Article
Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10.
R de Waal Malefyt,Carl G. Figdor,R.J.F. Huijbens,S Mohan-Peterson,Bruce Bennett,Janice Culpepper,Warren Dang,G Zurawski,J E de Vries +8 more
TL;DR: Results indicate that IL-13 has anti-inflammatory and important immunoregulatory activities and no additive or synergistic effects of IL-4 and IL- 13 on human monocytes were observed, suggesting that these cytokines may share common receptor components.
Journal ArticleDOI
The Emerging Role of CTLA-4 as an Immune Attenuator
TL;DR: It is demonstrated that CTLA-4 contributes to the risk of Grave's disease independently of human leukocyte antigen status or sex, and the number of independent confirmations that the CT LA-4 gene is associated with these two autoimmune diseases makes it likely that certain CTla-4 alleles may be risk factors for this disease.
Related Papers (5)
ICOS is essential for effective T-helper-cell responses.
Anna Tafuri,Arda Shahinian,Arda Shahinian,Friedhelm Bladt,Steve K. Yoshinaga,Manel Jordana,Andrew Wakeham,Andrew Wakeham,Louis-Martin Boucher,Louis-Martin Boucher,Denis Bouchard,Denis Bouchard,Vera S. F. Chan,Gordon S. Duncan,Gordon S. Duncan,Bernhard Odermatt,Alexandra Ho,Alexandra Ho,Annick Itie,Annick Itie,Tom Horan,John Whoriskey,Tony Pawson,Josef M. Penninger,Josef M. Penninger,Pamela S. Ohashi,Tak W. Mak,Tak W. Mak +27 more
T-cell co-stimulation through B7RP-1 and ICOS
Steven Kiyoshi Yoshinaga,John Whoriskey,Sanjay D. Khare,Ulla Sarmiento,Jane Guo,Tom Horan,Grace Shih,Ming Zhang,Marco A. Coccia,Tadahiko Kohno,Anna Tafuri-Bladt,David W. Brankow,Pauline Campbell,David Chang,Laura Chiu,Tianang Dai,Gordon S. Duncan,Gary Elliott,Ariela Hui,Susan McCabe,Sheila Scully,Arda Shahinian,Christine L. Shaklee,Gwyneth Van,Tak W. Mak,Giorgio Senaldi +25 more