Journal Article

Identification of Human NK17/NK1 Cells

Høglund, Rune A., Pandya, Abhilash D., Harbo, Hanne F., Al-Jaderi, Zaidoon, Maghazachi, Azzam A., Holmøy, Trygve, Norgauer, Johannes

2011

Overview

Natural killer (NK) cells have both cytolytic and immunoregulatory functions. We recently described that these cells release the inflammatory cytokines IL-17 and IFN-γ. However, the precise identity of the NK cell subset(s) that secrete these cytokines is not known. To isolate the cells secreting IL-17 and IFN-γ, we took advantage of the findings that Th17/Th1 cells express chemokine receptors. Therefore, CD56(+)NK cells were stained with antibodies against various chemokine receptors and intracellularly with antibodies toward IL-17 and IFN-γ. Consequently, we identified previously unrecognized subset of NK cells generated from normal human peripheral blood after activation with IL-2 but not PMA plus ionomycin. The cells are characterized by the expression of CD56(+) and CCR4(+), produce IL-17 and IFN-γ and are consequently named NK17/NK1 cells. They also express CD161, NKp30, NKp44, NKp46, NKG2D, CD158, CCL22, IL-2Rβ and the common γ chain but not CD127 or IL-23R. Further, they possess T-bet and RORγt transcription factors. Antibodies to IL-1β, IL-6, IL-21, or TGF-β1 do not inhibit IL-2-induced generation of NK17/NK1 cells, suggesting that IL-2 has the capacity to polarize these cells. Notably, NK17/NK1 cells are abundant in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) without activation, and are generated from the peripheral blood of these patients after activation with IL-2. NK17/NK1 cells identified here have not been previously described in healthy or MS patients.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Activation / Antibodies / Autoimmune diseases / Biology / Blood / CCL22 protein / CD56 antigen / Cerebrospinal fluid / Chemokine receptors / Chemokines / Cytokines / Enzyme-Linked Immunosorbent Assay / Flow Cytometry / Genotype & phenotype / Helper cells / Hospitals / Humans / Immunology / Immunoregulation / Inflammation / Interferon / Interferon-gamma - metabolism / Interleukin 17 / Interleukin 2 / Interleukin 2 receptors / Interleukin 21 / Interleukin 6 / Interleukin-1 - immunology / Interleukin-1 - metabolism / Interleukin-17 - immunology / Interleukin-17 - metabolism / Ionomycin / Killer cells / Killer Cells, Natural - immunology / Killer Cells, Natural - metabolism / Lymphocytes T / Medicine / Multiple sclerosis / Multiple Sclerosis - cerebrospinal fluid / Multiple Sclerosis - metabolism / Natural killer cells / Nervous system / NKG2 antigen / Patients / Peripheral blood / Physiology / Receptors / Regulation / Rodents / Stem cells / T cell receptors / Transcription factors / Transforming growth factor-b1 / Transforming growth factors / Zebrafish / γ-Interferon