title: TIP, a T-cell factor identified using high-throughput screening increases survival in a graft-versus-host disease model.
abstract: A coordinated effort combining bioinformatic tools with high-throughput cell-based screening assays was implemented to identify novel factors involved in T-cell biology. We generated a unique library of cDNAs encoding predicted secreted and transmembrane domain-containing proteins generated by analyzing the Human Genome Sciences cDNA database with a combination of two algorithms that predict signal peptides. Supernatants from mammalian cells transiently transfected with this library were incubated with primary T cells and T-cell lines in several high-throughput assays. Here we describe the discovery of a T cell factor, TIP (T cell immunomodulatory protein), which does not show any homology to proteins with known function. Treatment of primary human and murine T cells with TIP in vitro resulted in the secretion of IFN-gamma, TNF-alpha, and IL-10, whereas in vivo TIP had a protective effect in a mouse acute graft-versus-host disease (GVHD) model. Therefore, combining functional genomics with high-throughput cell-based screening is a valuable and efficient approach to identifying immunomodulatory activities for novel proteins.
authors.affiliation: Department of Preclinical Discovery, Human Genome Sciences, Inc., Rockville, MD 20850, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Fiscella
authors.forename: James W
authors.initials: JW
authors.lastname: Perry
authors.forename: Baiqin
authors.initials: B
authors.lastname: Teng
authors.forename: Michael
authors.initials: M
authors.lastname: Bloom
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Kam
authors.initials: K
authors.lastname: Leung
authors.forename: Laurie
authors.initials: L
authors.lastname: Pukac
authors.forename: Kimberly
authors.initials: K
authors.lastname: Florence
authors.forename: Alice
authors.initials: A
authors.lastname: Concepcion
authors.forename: Binjun
authors.initials: B
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Meng
authors.forename: Cecil
authors.initials: C
authors.lastname: Chen
authors.forename: Erika Cochrane
authors.initials: EC
authors.lastname: Elgin
authors.forename: Palanisamy
authors.initials: P
authors.lastname: Kanakaraj
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Kaufmann
authors.forename: Joelle
authors.initials: J
authors.lastname: Porter
authors.forename: Ricardo
authors.initials: R
authors.lastname: Cibotti
authors.forename: Yun
authors.initials: Y
authors.lastname: Mei
authors.forename: Joe
authors.initials: J
authors.lastname: Zhou
authors.forename: Guoxian
authors.initials: G
authors.lastname: Chen
authors.forename: Viktor
authors.initials: V
authors.lastname: Roschke
authors.forename: George
authors.initials: G
authors.lastname: Komatsoulis
authors.forename: Brian
authors.initials: B
authors.lastname: Mansfield
authors.forename: Steve
authors.initials: S
authors.lastname: Ruben
authors.forename: Indra
authors.initials: I
authors.lastname: Sanyal
authors.forename: Thi-Sau
authors.initials: TS
authors.lastname: Migone
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D020869:Gene Expression Profiling / Q000379:methods; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000196:embryology / Q000276:immunology; D051379:Mice / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020539:Sequence Analysis, Protein / Q000379:methods*; D013491:Suppressor Factors, Immunologic / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D011993:Recombinant Fusion Proteins; D013491:Suppressor Factors, Immunologic