TACI-BLyS signaling via B-cell-dendritic cell cooperation is required for naive CD8+ T-cell priming in vivo

Yaiza Diaz-de-Durana, George T. Mantchev, Richard J. Bram, Alessandra Franco

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)594-601
Number of pages8
JournalBlood
Volume107
Issue number2
DOIs
StatePublished - Jan 15 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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