Human lymphocyte activation gene-3 molecules expressed by activated T cells deliver costimulation signal for dendritic cell activation.
Data have been reported on the in vivo adjuvant role of soluble lymphocyte activation gene-3 (LAG-3) recombinant protein in mouse models and on its ability to support the in vitro generation of human, tumor-specific CTLs. In this study, we show that soluble human rLAG-3 protein (hLAG-3Ig) used in vitro as a single maturation agent induces phenotypic maturation of monocyte-derived dendritic cells and promoted the production of chemokines and TNF-alpha inflammatory cytokine. When given in association with optimal or suboptimal doses of CD40/CD40L, hLAG-3Ig functions as a strong costimulatory factor and induces full functional activation of monocyte-derived dendritic cells that includes the production of high level of IL-12p70. Moreover, evidence is here provided that this costimulatory function licensing dendritic cells to produce IL-12p70 is also a functional property of LAG-3 molecules when expressed in a physiological context by CD4(+) activated T cells. Altogether, these data show for the first time a role of LAG-3 in mediating dendritic cell activation when expressed on the T cell surface or released after specific Ag stimulation in the interspaces of immunological synapses.
Casati
Chiara
C
Unit of Immunotherapy of Human Tumor, Fondazione Instituto di Ricerca e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milano, Italy.
Camisaschi
Chiara
C
Novellino
Luisa
L
Mazzocchi
Arabella
A
Triebel
Frédéric
F
Rivoltini
Licia
L
Parmiani
Giorgio
G
Castelli
Chiara
C
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D016466:CHO Cells; D045744:Cell Line, Tumor; D018925:Chemokines / Q000096:biosynthesis; D018920:Coculture Techniques; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D041681:NIH 3T3 Cells; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D018925:Chemokines; D018836:Inflammation Mediators; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D000093322:Lymphocyte Activation Gene 3 Protein