title: T cell stimulator cells, an efficient and versatile cellular system to assess the role of costimulatory ligands in the activation of human T cells.
abstract: It is well established that full activation of T cells requires the interaction of the TCR complex with the peptide-MHC complex (Signal 1) and additional signals (Signal 2). These second signals are generated by the interaction of costimulatory ligands expressed on antigen presenting cells with activating receptors on T cells. In addition, T cell responses are negatively regulated by inhibitory costimulatory pathways. Since professional antigen presenting cells (APC) harbour a plethora of stimulating and inhibitory surface molecules, the contribution of individual costimulatory molecules is difficult to assess on these cells. We have developed a system of stimulator cells that can give signal 1 to human T cells via a membrane bound anti-CD3 antibody fragment. By expressing human costimulatory ligands on these cells, their role in T cell activation processes can readily be analyzed. We demonstrate that T cell stimulator cells are excellent tools to study various aspects of human T cell costimulation, including the effects of immunomodulatory drugs or how costimulatory signals contribute to the in vitro expansion of T cells. T cell stimulator cells are especially suited for the functional evaluation of ligands that are implicated in costimulatory processes. In this study we have evaluated the role of the CD2 family member CD150 (SLAM) and the TNF family member TL1A (TNFSF15) in the activation of human T cells. Whereas our results do not point to a significant role of CD150 in T cell activation we found TL1A to potently costimulate human T cells. Taken together our results demonstrate that T cell stimulator cells are excellent tools to study various aspects of costimulatory processes.
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Judith
authors.initials: J
authors.lastname: Leitner
authors.forename: Werner
authors.initials: W
authors.lastname: Kuschei
authors.forename: Katharina
authors.initials: K
authors.lastname: Grabmeier-Pfistershammer
authors.forename: Ramona
authors.initials: R
authors.lastname: Woitek
authors.forename: Ernst
authors.initials: E
authors.lastname: Kriehuber
authors.forename: Otto
authors.initials: O
authors.lastname: Majdic
authors.forename: Gerhard
authors.initials: G
authors.lastname: Zlabinger
authors.forename: Winfried F
authors.initials: WF
authors.lastname: Pickl
authors.forename: Peter
authors.initials: P
authors.lastname: Steinberger
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D001681:Biological Assay / Q000379:methods*; D045744:Cell Line, Tumor; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000276:immunology*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000276:immunology*
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D007155:Immunologic Factors; D010455:Peptides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1