Book ChapterDOI
Regulation of T Cell Activation by CD28 and CTLA4
Reads0
Chats0
TLDR
Although the mechanistic details remain to be elucidated, CD28 and CTLA4 appear to play important and complex roles in the control of immune homeostasis.Abstract:
T cell activation is initiated by engagement of the T cell receptor (TCR)-CD3 complex by antigen displayed by major histocompatibility complex (MHC) molecules expressed on the surface of an antigen presenting cell (APC). However, under most circumstances, this initial signal is insufficient to induce a proliferative response. TCR engagement in the absence of a second or costimulatory signal can lead to a state of anergy or cell death1. CD28 is a T cell surface receptor capable of providing this critical second signal following ligation of the B7 family of counter-receptors that are expressed on APCs2,3. This interaction provides not only proliferative signals, but also crucial survival signals that are important for both initiation and maintenance of an immune response4,5.read more
Citations
More filters
Journal ArticleDOI
CD28 and CTLA-4 coreceptor expression and signal transduction.
TL;DR: The current knowledge of the CD28 and CTLA‐4 signaling mechanisms [involving phosphatidylinositol 3 kinase (PI3K), growth factor receptor‐bound protein 2 (Grb2), Filamin A, protein kinase C θ (PKCθ), and phosphatases] that control T‐cell immunity are outlined.
Journal ArticleDOI
Akt provides the CD28 costimulatory signal for up-regulation of IL-2 and IFN-gamma but not TH2 cytokines.
TL;DR: It is shown that the serine-threonine kinase Akt can provide a costimulatory signal for RE/AP activation that is indistinguishable from the signal provided by CD28, providing evidence that CD28 costimulation of different cytokines is mediated by discrete signaling pathways, one of which includes Akt.
Journal ArticleDOI
Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients
Filemon K. Tan,Xiaodong Zhou,Maureen D. Mayes,Pravitt Gourh,Xinjian Guo,C. Marcum,Li Jin,Frank C. Arnett +7 more
TL;DR: Although the SSc PBC gene expression profile demonstrated some parallels with the lupus interferon gene signature, there was also increased expression of transcripts encoding proteins that target PBCs to the endothelium, which might be relevant to the vasculopathy of SSc.
Journal ArticleDOI
Bispecific antibodies in cancer therapy.
TL;DR: Based upon in vitro and animal studies, a number of Phase I and II clinical trials have been initiated to test whether bispecific antibodies could redirect immune effectors against tumor cells in cancer patients and showed beneficial effects in some patients.
Journal Article
Specific immune induction following DNA-based immunization through in vivo transfection and activation of macrophages/antigen-presenting cells.
TL;DR: The presence of activated macrophages or dendritic cells in the blood lymphocyte pool and peripheral tissues of animals inoculated with DNA expression cassettes is demonstrated and indicates that these cells function as APC and can activate naive T lymphocytes.
References
More filters
Journal ArticleDOI
The Fas Death Factor
Shigekazu Nagata,Pierre Golstein +1 more
TL;DR: Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells.
Journal ArticleDOI
The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis.
Naoto Itoh,Shin Yonehara,Ai Ishii,Minako Yonehara,Sei Ichi Mizushima,Masazumi Sameshima,Atsushi Hase,Yoshiyuki Seto,Shigekazu Nagata +8 more
TL;DR: Complementary DNAs encoding the cell surface antigen Fas were isolated from a cDNA library of human T cell lymphoma KT-3 cells and revealed that the molecule coding for the Fas antigen determinant is a 319 amino acid polypeptide with a single transmembrane domain.
Journal ArticleDOI
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
Paul Waterhouse,Josef M. Penninger,Emma Timms,Andrew Wakeham,Arda Shahinian,Kelvin P. Lee,Craig B. Thompson,Henrik Griesser,Tak W. Mak +8 more
TL;DR: Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation, and is vital for the control of lymphocyte homeostasis.
Journal ArticleDOI
CTLA-4 can function as a negative regulator of T cell activation
Theresa L. Walunas,Deborah J. Lenschow,Christina Y. Bakker,Peter S. Linsley,Gordon J. Freeman,Jonathan Green,Craig B. Thompson,Craig B. Thompson,Jeffrey A. Bluestone +8 more
TL;DR: Results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function.
Journal ArticleDOI
A cell culture model for T lymphocyte clonal anergy
TL;DR: The T cell enters an unresponsive state known as clonal anergy in which the T cell is incapable of producing its own growth hormone, interleukin-2, on restimulation.
Related Papers (5)
Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease
H Ueda,Howson Jmm.,Laura Esposito,Joanne M. Heward,Hywel Snook,Giselle Chamberlain,Dan Rainbow,Hunter Kmd.,Anne Smith,G Di Genova,G Di Genova,Mathias H. Herr,Mathias H. Herr,Ingrid Dahlman,Ingrid Dahlman,F Payne,Deborah J. Smyth,Christopher E. Lowe,Twells Rcj.,Sarah Howlett,Barry C. Healy,Sarah Nutland,Helen E. Rance,Vincent H. Everett,Luc J. Smink,A C Lam,Heather J. Cordell,Neil Walker,C Bordin,John S. Hulme,Costantino Motzo,Francesco Cucca,J F Hess,Michael L. Metzker,Michael L. Metzker,Jane Rogers,Simon G. Gregory,Amit Allahabadia,Amit Allahabadia,R Nithiyananthan,Eva Tuomilehto-Wolf,Jaakko Tuomilehto,Polly J. Bingley,Kathleen M Gillespie,Dag E. Undlien,Kjersti S. Rønningen,Cristian Guja,Constantin Ionescu-Tirgoviste,David A. Savage,Alexander P. Maxwell,Dennis Carson,Christopher Patterson,Jayne A. Franklyn,David Clayton,Laurence B. Peterson,Linda S. Wicker,John A. Todd,Gough Scl. +57 more