Research focus of our laboratory is to identify and characterize co-signal molecules which play key roles in the control of T cell activation and deactivation. Co-signal molecules are essential for the communication of a T cell with virtually all other host cells. During cell-cell contact, specific recognition occurs between co-signal molecules and triggers biochemical signaling, which leads to cascades of transcription and expression of downstream genes in the nucleus. Therefore, co-signaling molecules are among the earliest responding elements of the immune system to antigens. A hallmark for co-signal molecules is that their functions are entirely dependent on TCR signals and the role of co-signal molecules is to control the TCR signal. In the absence of sufficient TCR signaling, co-signal molecules lose their function or function aberrantly. The majority of co-signal molecules are members of the immunoglobulin (Ig) and tumor necrosis factor (TNF) superfamilies. Based on the functional outcomes, co-signal molecules can be further categorized as costimulators or positive costimulatory molecules that enhance TCR-mediated responses, and coinhibitors or negative costimulatory molecules that inhibit TCR-mediated responses. The main interest of our laboratory is biochemical, structural and functional studies of co-signal molecules. We are also interested in defining signaling events that induces activation and deactivation of naﶥ and mature effector T cells. By precise manipulation of these cell surface molecular pathways, we hope to develop new strategies to treat cancer, autoimmune diseases, viral infection and transplantation rejection.

Dong H, Zhu G, Tamada K, Flies DB, van Deursen JMA and Chen L. (2004) B7-H1 determines accumulation and deletion of intrahepatic CD8+ T lymphocytes. Immunity 276:26421 [PubMed]

Chen L. (2004) Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat. Rev. Immunol. 1:463 [PubMed]

Sica GL, Choi IH, Zhu G, Tamada K, Wang S, Tamura H, Chapoval AI, Flies DB, Bajorath J and Chen L. (2003) B7-H4, a molecule of the B7 family, negatively regulates T-cell immunity. Immunity 21:3935 [PubMed]

Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E and Chen L. (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nature Medicine 276:27806 [PubMed]

Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Dong H, Sica GL, Zhu G, Tamada K and Chen L. (2001) B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Nature Immunol. 108:331 [PubMed]

Tamada K, Shimozaki K, Chapoval AI, Zhu G, Sica G, Flies D, Boone T, Hsu H, Fu YX, Nagata S, Ni J and Chen L. (2000) Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway. Nature Medicine 16:545-9 [PubMed]