Mouse T cells receive costimulatory signals from LIGHT, a TNF family member.
LIGHT is a tumor necrosis factor (TNF) family member and is expressed on activated T cells. Its known receptors are TR2 and LTbetaR on the cell surface, and TR6/DcR3 in solution. TR6/DcR3 is a secreted protein belonging to the TNF receptor family. It binds to Fas ligand (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 upon T-cell receptor (TCR) ligation. A monoclonal antibody against LIGHT similarly costimulated 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-cross-linking, TCR and rafts rapidly formed caps where they colocalized. LIGHT rapidly congregated and colocalized with the aggregated rafts. This provided a molecular base for the signaling machinery of LIGHT to interact with that of TCR. Indeed, LIGHT cross-linking enhanced p44/42 mitogen-activated protein kinase activation after TCR ligation. This study reveals a new function and signaling event of LIGHT.
Shi
Guixiu
G
Laboratory of Transplantation Immunology, Research Center, Centre hospitalier de l'Universite de Montreal (CHUM)-Notre Dame Hospital, Pavilion DeSeve, 1560 Sherbrooke Street E., Montreal, Quebec H2L 4M21, Canada.
Luo
Hongyu
H
Wan
Xiaochun
X
Salcedo
Theodora W
TW
Zhang
Jun
J
Wu
Jiangping
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000378:metabolism; D021962:Membrane Microdomains / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; C505914:TNFSF14 protein, human; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one