CD137/CD137L EXPRESSION AND SIGNALING IN IN VITRO MODELS OF HUMAN AIRWAY EPITHELIUM, DENDRITIC CELLS AND T-CELLS.

This study by scientists at MatTek Corp. demonstrated that MatTek’s EpiAirway in vitro human airway tissue model and MatTek’s Human Dendritic Cells are excellent in vitro models for studying the signaling of CD137, a potent T-cell co-stimulatory molecule related to human diseases including cancer and asthma. CD137 is a potent T-cell co-stimulatory molecule that has been identified as a promising target for immunotherapy of cancer and autoimmune diseases including asthma. Agonistic CD137 antibodies have been shown to produce regression of cancerous tumors and reversal of asthma in murine models of these diseases. Although CD137 is most often associated with co-stimulation of T-cells, its expression has also been reported in other cell types including dendritic cells (DCs), and airway epithelium. In the current studies, expression and function of CD137 and its ligand (CD137L) was investigated in in vitro human model systems of well differentiated airway epithelium (EpiAirway™) and cord blood derived T-cells and DCs (Human Dendritic Cells). Normal human bronchial epithelial cells (NHBE) were cultured on microporous membrane inserts at the air liquid interface to produce the well differentiated pseudostratified airway epithelia model. DCs were derived from cord blood CD34+ progenitor cells. Expression of CD137 and CD137L were investigated in the EpiAirway cultures and human DCs (mixture of plasmacytoid CD123+ and myloid CD11c+ cells) by RT-PCR. Both EpiAirway and DCs expressed CD137 and CD137L mRNA. EpiAirway expressed High levels of CD137L and relatively low levels of CD137. DCs expressed high levels of both CD137 and CD137L. Treatment of DCs with agonistic CD137 antibody induced secretion of IL-12, while treatment of T-cells with the CD137 Ab induced secretion of INF-ã. These experiments demonstrate expression and function of CD137 and CD137L in human model systems. These models will be useful for gaining additional knowledge of human CD137/CD137L signaling related to human diseases including cancer and asthma.

AIR-100, Agnostic CD137 antibody, CD137, CD137L ligand, Co-stimulatory molecule, DC-100, Dendritic cells, EpiAirway, IL-12, INF-gamma, T-cell co-stimulatory molecule, TC-100

Cautery instrument, MMP inhibitor