TY - JOUR
T1 - TACI-BLyS signaling via B-cell-dendritic cell cooperation is required for naive CD8+ T-cell priming in vivo
AU - Diaz-de-Durana, Yaiza
AU - Mantchev, George T.
AU - Bram, Richard J.
AU - Franco, Alessandra
PY - 2006/1/15
Y1 - 2006/1/15
N2 - 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. BLyShigh 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.
AB - 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. BLyShigh 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.
UR - http://www.scopus.com/inward/record.url?scp=30444439583&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30444439583&partnerID=8YFLogxK
U2 - 10.1182/blood-2004-12-4708
DO - 10.1182/blood-2004-12-4708
M3 - Article
C2 - 16195331
AN - SCOPUS:30444439583
SN - 0006-4971
VL - 107
SP - 594
EP - 601
JO - Blood
JF - Blood
IS - 2
ER -