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PAMP mediated activation of type II NKT cells

Konferensbidrag (offentliggjort, men ej förlagsutgivet)
Författare Sai Kiran Sedimbi
Linda Löfbom
Ulf Yrlid
Susanna Cardell
Publicerad i 6th International Symposium on CD1d and NK T cells, September 23-27, 2011, Chicago, IL, USA
Publiceringsår 2011
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Språk en
Ämnesord Type II NKT cells, Innate activation, TLR
Ämneskategorier Immunologi inom det medicinska området

Sammanfattning

Type 2 NK T cells are known to have immuno-stimulatory/regulatory effects on innate and adaptive immune responses to infections, tumors and autoimmunity. However, there is a paucity of information regarding the mechanism of activation of type 2 NK T cells in various immune responses. We aim to identify the signals required for activation of type 2 NK T cells by pathogen associated molecular patterns (PAMPs). Using type 2 NK T cells from a transgenic mouse model (24αβ B6: over expressing Vα3.2/Vβ9 type 2 NK T cells), we performed co-culture experiments with enriched primary type 2 NK T cells and bone marrow derived dendritic cells (DC) from mice that were WT or harbouring various gene deletions. Several TLR ligands activated the type 2 NK T cells in the co-cultures. The experiments revealed that type 2 NK T cells were not activated directly by PAMPs, but required the presence of antigen presenting cells such as DC. Transwell experiments suggest that activation occurred in a cell-contact dependent fashion. Further, we find that IL12 was absolutely essential for activation, while type I interferons appear to be dispensible. Surprisingly, CD1d was not required for type 2 NK T cell activation by PAMPs. Our results suggest that in addition to IL-12, other DC mediated signals were required for the CD1d-independent activation of type 2 NK T cells by PAMPs. Ongoing studies are investigating further which signals are required for NKT cell activation and the type of immune response induced.

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