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Defective CD40‐dependent antigen cross‐priming of CD8 + T cells in mice with conditional deletion of NF‐κB‐inducing kinase (146.11)
Author(s) -
Katakam Anand,
Brightbill Hans,
Franci Christian,
Wu Lawren,
Mellman Ira,
Delamarre Lelia,
Austin Cary
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.146.11
Subject(s) - cd40 , priming (agriculture) , acquired immune system , biology , t cell , microbiology and biotechnology , cross presentation , cytotoxic t cell , cd11c , immune system , cd8 , antigen presenting cell , immunology , in vitro , phenotype , genetics , germination , botany , gene
Dendritic cells (DCs) link innate and adaptive immunity, using a host of innate immune and inflammatory receptors to respond to pathogens and inflammatory stimuli. While canonical NF‐κB signaling within DCs is clearly important for many of these responses, the role of non‐canonical NF‐κB signaling via the serine/threonine kinase NIK needs clarification. To investigate the function of NIK in DC stimulus responses and immunity, we generated transgenic mice with targeted NIK deletion in CD11c + DCs. We observe that conditional deletion of NIK impairs CD40‐dependent cross‐priming of naïve CD8 T cells in vivo and deficient CD40‐stimulated antigen cross‐presentation and IL‐12p40 secretion by splenic‐derived DCs in vitro . In human monocyte‐derived DCs after siRNA silencing of NIK in vitro , we observe a similar IL‐12p40 secretion defect. These findings suggest that NIK serves to transmit a ‘DC licensing’ signal from CD4 T helper cells to naïve CD8 T cells during antigen cross‐priming of a CD8 T cell response.