1. TIP, a T-cell factor identified using high-throughput screening increases survival in a graft-versus-host disease model.
- Author
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Fiscella M, Perry JW, Teng B, Bloom M, Zhang C, Leung K, Pukac L, Florence K, Concepcion A, Liu B, Meng Y, Chen C, Elgin EC, Kanakaraj P, Kaufmann TE, Porter J, Cibotti R, Mei Y, Zhou J, Chen G, Roschke V, Komatsoulis G, Mansfield B, Ruben S, Sanyal I, and Migone TS
- Subjects
- Adjuvants, Immunologic chemistry, Adjuvants, Immunologic genetics, Adjuvants, Immunologic metabolism, Animals, Cell Line, Gene Expression Profiling methods, Graft vs Host Disease immunology, Graft vs Host Disease metabolism, Humans, Kidney chemistry, Kidney embryology, Kidney immunology, Mice genetics, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins immunology, Recombinant Fusion Proteins metabolism, Suppressor Factors, Immunologic genetics, Suppressor Factors, Immunologic immunology, T-Cell Antigen Receptor Specificity genetics, T-Lymphocytes chemistry, T-Lymphocytes drug effects, T-Lymphocytes immunology, Transfection methods, Graft vs Host Disease drug therapy, Sequence Analysis, Protein methods, Suppressor Factors, Immunologic administration & dosage, Suppressor Factors, Immunologic chemistry, T-Lymphocytes metabolism
- 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.
- Published
- 2003
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