TACI-BLyS signaling via B-cell-dendritic cell cooperation is required for naive CD8+ T-cell priming in vivo.
We demonstrated that B-cell-dendritic cell (DC) interactions via transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) and B-lymphocyte stimulator (BLyS) provide an early signal critical to generate adequate numbers of mature antigen presenting cells (APCs) to prime naive CD8(+) T cells (CTLs) in vivo. Evidence that B cells are required for efficient CTL generation in mice and that reconstitution with wild-type but not TACI-knockout B cells restored normal CTL responses support our conclusion. Moreover, low doses of a TACI fusion protein (TACI-Fc) that express the extracellular domain of TACI (amino acid [aa] 1-126) restored CTL priming in B-cell-deficient mice in vivo and induced DC maturation in vitro. In fact, following interactions with B cells, splenic DCs rapidly express the CD86 costimulatory molecule, to an extent comparable to the exposure to antigenic stimuli. BLyS(high) peptide-pulsed bone marrow-derived DCs, used as vaccines in vivo, cannot generate CTLs in B-cell-deficient and TACI-deficient mice, strongly supporting a need for B-cell-DC cooperation through TACI-BLyS during CTL first encounter with antigens in vivo.
Diaz-de-Durana
Yaiza
Y
Torrey Pines Institute for Molecular Studies, San Diego, CA, USA.
Mantchev
George T
GT
Bram
Richard J
RJ
Franco
Alessandra
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D007114:Immunization; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D053303:Transmembrane Activator and CAML Interactor Protein; D014611:Vaccination; D001613:beta 2-Microglobulin / Q000235:genetics / Q000502:physiology
D051940:B7-2 Antigen; D019013:CD40 Antigens; D007376:Interleukin-2; D008565:Membrane Proteins; D010446:Peptide Fragments; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C486361:Tnfrsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D001613:beta 2-Microglobulin; D015847:Interleukin-4