The development and differentiation of NK cells are highly noted in recent years.In addition to the peripheral blood,spleen and bone marrow,the liver,lymph nodes and thymus are also considered as important organs for differentiation of NK cell precursors(NKPs).Human NK cell subset CD56bright is enriched in secondary lymphoid tissues and non-lymph tissues;NK subset cell CD56dim can migrate to peripheral inflammatory region.Activating receptors on NK cells include cytokine receptors,integrin receptors,natural cytotoxic receptors,immunoglobulin-like killer receptors,and many new receptors and ligands different from the aforementioned receptor families.In the process of tumor progression,NK cells can directly recognize malignant cells via "internal recognition" and be activated;they can also be activated by accessory cells such as monocytes,macrophages and dentritic cells.DC cells can trigger the activation of NK cells,in which the reverse signal transduction of IL-15R-IL-15 plays an important role.Great progression has been made in NK cell-based immunotherapy of tumor,in particular there are many new ways in NK cell innate recognition-based tumor biotherapy.

Natural killer cells are the key effector cells in innate immune response,playing the role in pathogen clearance and tumor immunosurveillance by cytokine secretion and cytotoxicity.Hematopoietic stem cells go through developmental intermediates to generate mature NK cells under the progressive regulation of extrinsic factors and intrinsic factors.In the past thirty years, great progresses have been made in the developmental progress,niches,regulation of NK cells and the relationship between NK cells and dis-eases.In this review,we will discuss in detail the molecular mechanisms of NK cell development and the diseases caused by functional compromise of NK cells.

Type Ⅱ innate lymphoid cells is an emerging family of innate lymphocytes mainly distributed in mucosal tissues such as the lungs,intestines,skin,etc.These cells are capable of producing Th2-type cytokines including IL-5 and IL-13 in response to IL-25 and IL-33.ILC2s has attracted much attention for its important roles in anti-infection immunity and allergic diseases in respiratory tract.Studies have shown that ILC2s represented a crucial source of Th2-type cytokines and could regulate the adaptive immune response in allergic airway diseases.Meanwhile,ILC2s was able to fulfill vital functions in parasite clearance, anti-virus infection and subsequent tissue repair.Therefore,research in ILC2s phenotype,development and function has great practical significance.This paper reviews the definition, classification, developmental regulation of ILC2s with a particular focus on its role in respiratory mucosal homeostasis and lung-related diseases.

A new NK cell subset with antigen presentation function was recently found and called as interferon-producing killer dendritic cells (IKDC cells).These cells co-express surface markers of NK cells and DCs;functionally,they can secrete interferons,kill target cells and have antigen-presenting ability.IKDCs extensively exist in almost all lymphoid tissue or organs with similar phenotype,but recent studies indicated that IKDCs were developmently not from DC cells but from NK cells,the conclusion of which is still in its early stage.The discovery of IKDC will be help to understand the link between innate and adaptive immunity.

Recent reports have indicated that NK cells may have the function of immunological memory in common with cells of the adaptive immune system."Memory" NK cells move through the four phases of the adaptive immune response — proliferation,contraction,memory and recall which was similar to the T-cell responses."Memory" NK cells have special phenotypes.During MCMV infection,"memory" NK cells showed a greater expression of Ly49H,KLRG1,CD43 and Ly6C,and a decreased expression of CD27.In hapten (DNFB)-induced contact hypersensitivity model,the sorted liver NK cell subsets with the phenotype of Thy-1+Ly49C-I+ had the transferable memory activity,occupying around 10% of hepaedtic NK cells.These Ly49H+"memory" NK cells might produce more IFN-gamma ex vivo in response to plate-bound antibody against NK1.1 or Ly49H.Degranulation by Ly49H+ "memory" NK cells was also enhanced,as assessed by CD107a expression after ex vivo stimulation with anti-NK1.1."Memory" NK cells may move through the same migratory routes and adhesion pathways during the priming and effector phases of DNFB-primed Rag2-/-mice as conventional T cells of normal mice.Until now,it is not clear about the requirements for the triggering,regulation and maintenance of NK cell memory,but it is absolutely clear that "Memory" NK cells must play important role in host defense against pathogens.

NK cells can be divided into two subsets based on CD27 expression:CD27hiNK cells and CD27loNK cells.NK cells can be further divided into four subsets based on CD27 and CD11b: CD11bloCD27lo,CD11bloCD27hi,CD11bhiCD27hi and CD11bhiCD27lo.These subsets in different development stages have their own phenotypes and functions.In mice,NK cell developing pathway is through CD11bloCD27lo→CD11bloCD27hi→CD11bhiCD27hi→CD11bhiCD27lo.CD27 can also be used to divide human NK cells into two subsets which are comparable to those of mice.

The mucosal tissues form the interface between the outside world and the sterile environment of the body.Innate immunity plays a critical role in the maintenance of mucosal homeostasis.Recently,a new subset of innate immune cells named NK-22 has been discovered to reside at tonsil and intestine both in human and mice.NK-22 cells share features with both natural killer (NK) cells and lymphoid tissue-inducing (LTi) cells.NK-22 cells express a variety of NK cell receptors and phenotypically resemble that of immature NK cells (iNKs).However,they are quite different from NK cells in function and development.NK-22 cells lack conventional NK cell cytotoxic function and produce IL-22 instead of IFN-?.It is currently considered that NK-22 cells are not a subset of NK cells.They develop from LTi cells and the development process depends on ROR?t and commensal microflora.NK-22 cells are involved in immune protection against the pathogen Citrobacter rodentium.The IL-22 secreted by NK-22 cells contributes to epithelial cell resistance to injury and mucosal tissue repair after microbial infection.

thymus.It is not clear why and how these distribution exist,which is possibly correlated to recruitment,homing,subset,and microenvironment of NK cells in each tissue or organ.

Large scale preparation of human IL-2 mRNA was obtained from human spleen cells stimulated with PHA+TPA at the peak of IL-2 mRNA transcription. Full length of IL-2 mRNA was translated in wheat germ extract to produce bioactive IL-2 (tIL-2). The IL-2 mRNA was about 14 S depending on the 7 M Urea-SDS-PAGE, and recovried from gel and translated in vitro. The elute curve of tIL-2 was the same as that of recombinant IL-2 (rIL-2) and natural IL-2 (nIL-2), the molecular weight of tIL-2 was about 14.000 dalton. The translational process of IL-2 mRNA in vitro was inhibited when RNA was cultured with RNase or translated product was cultured with proteinase, proving a standard in-vitro translation.

Under stimulation of PHA,PHA + TPA,or PHA + PTS the time ke-netics of DNA,RNA,protein synthesis and lymphokine secretion by human lymph node cell expressed different responses. The PTS did not increase the DNA and RNA synthesis, but increased the protein synthesis ( 60% ) . TPA increased the RNA synthesis ( 18% ) , therefor increased the protein synthesis ( 40% ) . Both of TPA and PTS increased the production of 5 kinds of lymphokines (IL-1 , IL-2 , IL-3, BCGF, TFNr). We infer that PTS and TPA increase the lymphokine production through different gene regulation. TPA Promotes the translation of lymphokine mRNA。