We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
TIP, a T-cell factor identified using high-throughput screening increases survival in a graft-versus-host disease model.
- Authors
Fiscella, Michele; Perry, James W.; Teng, Baiqin; Bloom, Michael; Zhang, Chen; Leung, Kam; Pukac, Laurie; Florence, Kimberly; Concepcion, Alice; Liu, Binjun; Meng, Ying; Chen, Cecil; Cochrane Elgin, Erika; Kanakaraj, Palanisamy; Kaufmann, Thomas E.; Porter, Joelle; Cibotti, Ricardo; Mei, Yun; Zhou, Joe
- 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-γ, TNF-α, 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.
- Subjects
T cells; GRAFT versus host disease; MICROBIOLOGICAL assay
- Publication
Nature Biotechnology, 2003, Vol 21, Issue 3, p302
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt797