Selective loss of c-Rel compromises dendritic cell activation of T lymphocytes.
Dendritic cells initiate the immune response by presenting antigen in the context of varying levels of costimulation. The maturation state of the dendritic cell determines the quantity and quality (Th1, Th2) of the subsequent T cell response. Members of the NF-kappaB family of transcription factors have previously been implicated in dendritic cell development. Here, we used a mouse with a homozygous c-Rel deletion to investigate the role of c-Rel in the function of bone marrow derived dendritic cells. When direct presentation was evaluated, we found c-Rel(-/-) dendritic cells induce less allogeneic T cell stimulation than c-Rel(+/+) dendritic cells. In addition, T cell encounters with c-Rel(-/-) dendritic cells generate less IFN-gamma and IL-4 when compared to those with c-Rel(+/+) DCs. A similar degree of functional compromise was observed in antigen-specific T cells that were stimulated by c-Rel(-/-) dendritic cells. Functional deficits were not linked to differences in the ability to undergo maturation per se, as LPS exposure induced similar morphologic and cell surface changes in both c-Rel(+/+) and cRel(-/-) DCs. Although LPS induced a compensatory increase in the nuclear activity of fellow NF-kappaB family members, RelB and p65, LPS exposure was unable to negate the deficiencies in autologous T cell proliferation and cytokine production associated with the loss of c-Rel in dendritic cells. Taken together, our study supports a unique and non-redundant role for c-Rel in dendritic cell costimulatory capacity.
Boffa
Daniel J
DJ
The Department of Medicine, The New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, NY 10021, USA.
Feng
Biao
B
Sharma
Vijay
V
Dematteo
Ronald
R
Miller
George
G
Suthanthiran
M
M
Nunez
Rafael
R
Liou
Hsiou-Chi
HC
D000818:Animals; D003713:Dendritic Cells / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D008070:Lipopolysaccharides; D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel