Selective loss of c-Rel compromises dendritic cell activation of T lymphocytes Journal Article


Authors: Boffa, D. J.; Feng, B.; Sharma, V.; DeMatteo, R.; Miller, G.; Suthanthiran, M.; Nunez, R.; Liou, H. C.
Article Title: Selective loss of c-Rel compromises dendritic cell activation of T lymphocytes
Abstract: 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 antologous 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. (C) 2003 Elsevier Science (USA). All rights reserved.
Keywords: survival; apoptosis; transcription factors; cytokines; dendritic cells; antigen; nf-kappa b; receptor; presentation; t lymphocytes; gene-expression; nf-kappa-b; maturation; costimulation; differential expression; c-rel; b/rel family
Journal Title: Cellular Immunology
Volume: 222
Issue: 2
ISSN: 0008-8749
Publisher: Elsevier Inc.  
Date Published: 2003-04-01
Start Page: 105
End Page: 115
Language: English
ACCESSION: WOS:000183995600003
DOI: 10.1016/S0008-8749(03)00114-X
PROVIDER: wos
PUBMED: 12826080
Notes: Article -- Source: Wos
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MSK Authors
  1. Rafael Nunez
    13 Nunez
  2. George Miller
    18 Miller
  3. Ronald P DeMatteo
    615 DeMatteo