CD4 T cell priming in dendritic cell-deficient mice.
Bone marrow (BM) chimeras (BMC) generated from mice carrying a null (-/-) mutation in the relB gene of the NF-kappaB family represent an ideal model for in vivo studies on the role of dendritic cells (DC) in the adaptive immune response. The spleen and lymph nodes (LN) of relB(-/-) BMC contain a small number of residual DC, mainly CD8alpha(+), that fail to up-regulate MHC class II and co-stimulatory molecules after stimulation in vitro. Moreover, residual spleen DC of relB(-/-) BMC have a 4-fold decrease in the ability to uptake and process soluble model antigen, ovalbumin (OVA), and failed to prime CD4 and CD8 T cells in vitro and in vivo. In addition, they also failed to present OVA peptide to OT-II transgenic T lymphocytes at a normal 1:10 (stimulator:responder) cell ratio. In spite of these multiple DC defects, relB(-/-) BMC immunized with plasmid DNA targeted to the spleen as the site of immune induction develop a specific CD4(+) T cell response comparable to that of relB competent mice. These data demonstrate that CD4( +) T cells can be primed in the absence of functional DC and suggest that relB may gauge the T cell response in vivo.
Castiglioni
Paola
P
Department of Medicine and Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla CA 92093-0837, USA.
Lu
Christina
C
Lo
David
D
Croft
Michael
M
Langlade-Demoyen
Pierre
P
Zanetti
Maurizio
M
Gerloni
Mara
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB