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Prepublished online as a Blood First Edition Paper on June 21, 2002; DOI 10.1182/blood-2002-05-1404.
Submitted May 14, 2002
Accepted June 11, 2002
MOUSE T CELLS RECEIVE COSTIMULATORY SIGNALS FROM LIGHT, A TNF FAMILY MEMBER
Guixiu Shi, Hongyu Luo, Xiaochun Wan, Theodora W Salcedo, Jun Zhang, and Jiangping Wu*
Laboratory of Transplantation Immunology, Research Center, Centre Hospitalier de l'Universitaire de Montreal, Montreal, PQ, Canada
Human Genome Sciences Inc, Rockville, Maryland, USA
Laboratory of Transplantation Immunology, Research Center, Centre Hospitalier de l'Universitaire de Montreal, Montreal, PQ, Canada; Department of Surgery, McGill University, Montreal, PQ, Canada
* Corresponding author; email: jianping.wu{at}umontreal.ca.
LIGHT is a TNF family member, and is expressed on activated T cells. Its known receptors are TR2 and LTßR on the cell surface, and DcR3/TR6 in solution. DcR3/TR6 is a secreted protein belonging to the TNF receptor family. It binds to FasL, LIGHT and TL1A, all of which are TNF family members. In the present study, we report that solid phase TR6-Fc costimulated proliferation, lymphokine production and cytotoxicity of mouse T cells in the presence of TCR ligation. A monoclonal Ab against LIGHT similarly costimulated the mouse T cells in their proliferation response to TCR ligation. These data suggest LIGHT, although a ligand, can receive costimulation when expressed on the T-cell surface. Mechanistically, when T cells were activated by TCR and CD28 co-crosslinking, TCR and rafts rapidly formed caps where they co-localized. LIGHT rapidly congregated and co-localized with the aggregated rafts. This provides a molecular base for the signaling machinery of LIGHT to interact with that of TCR. Indeed, LIGHT crosslinking enhanced p44/42 MAPK kinase activation after TCR ligation. This study reveals a new function and signaling event of LIGHT.
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