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Increased NK‐DC co‐operation and resulting adaptive immune response after HSV infection involves TLR signaling
Author(s) -
Woolard Stacie Necole,
Nandakumar Subhadra,
KurtJones Evelyn,
Kumaraguru Uday
Publication year - 2008
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.22.1_supplement.672.45
Subject(s) - cd80 , interleukin 12 , cd86 , immunology , biology , immune system , microbiology and biotechnology , interleukin 21 , cd40 , chemokine , acquired immune system , cytokine , t cell , cytotoxic t cell , in vitro , biochemistry
The induction of DC maturation by TLR ligands is considered as a pivotal link between innate and adaptive immune responses. This renders the DCs capable of directing the T cell response. NK cells also express some of the TLRs expressed by DCs. It is our hypothesis that HSV orchestrates the early event of NK cell and DC interaction through TLR mediated signaling. To test this, we used autologous DCs that were stimulated with various TLR ligands described to be associated with HSV infection (TLR 2, 3, and 9) or cytokines or virus. NK cells (generated from NK precursors or isolated from lymphoid organs) were co‐cultured for 18 hours in the presence or absence of these DCs and later analyzed for their phenotypic changes (CD25, CD69, Chemokine receptors CCR7 and CxCR3), cytokine production (IFN‐γ), and cytotoxicity (YAC cells). NK cells’ acquired cytolytic ability was also tested against Daudi target cells which are usually resistant to NK killing. DCs and NK cells generated from bone marrows of MyD88 knockout were used similarly and in mix and match combination. The DCs were analyzed for upregulation of activation and co‐stimulatory markers (CD80, CD86, MHC class I and II, CD40 etc.). They were also analyzed for their stimulatory activity after osmatically loading of ova protein or HSV gB protein and measuring their ability to induce activation and proliferation of peptide specific T cells. The results suggest that the initial interaction between the DCs and NK cells are largely due to signaling through the TLR. If the cells lacked MyD88 signaling their productive interaction was greatly diminished. Acknowledgement: ETSU startup funds to U. Kumaraguru