TIP, a T-cell factor identified using high-throughput screening increases survival in a graft-versus-host disease model

Nat Biotechnol. 2003 Mar;21(3):302-7. doi: 10.1038/nbt797. Epub 2003 Feb 24.


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.

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / metabolism
  • Animals
  • Cell Line
  • Gene Expression Profiling / methods
  • Graft vs Host Disease / drug therapy*
  • 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
  • Sequence Analysis, Protein / methods*
  • Suppressor Factors, Immunologic / administration & dosage*
  • Suppressor Factors, Immunologic / chemistry*
  • Suppressor Factors, Immunologic / genetics
  • Suppressor Factors, Immunologic / immunology
  • T-Cell Antigen Receptor Specificity / genetics
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transfection / methods


  • Adjuvants, Immunologic
  • Recombinant Fusion Proteins
  • Suppressor Factors, Immunologic