Natural Killer Cells In Pathogenesis Research Articles

The role of natural killer cells in pathogenesis of autoimmune diseases.

There is growing evidence that NK cell-mediated immunoregulation plays an important role in the control of autoimmunity. NK cells are a subset of lymphocytes that generally contribute to innate immunity but have also a great impact on the function of T and B lymphocytes. The major role of NK cells is cytotoxic reaction against neoplastic, infected and autoreactive cells, but they regulatory function seems to play more important role in the pathogenesis of autoimmune diseases. Numerous studies suggested the involvement of NK cells in pathogenesis of such a common autoimmune diseases as juvenile rheumatoid arthritis, type I diabetes and autoimmune thyroid diseases. The defects of NK cells regulatory function as well as cytotoxic abilities are common in patients with autoimmune diseases with serious consequences including HLH hemophagocytic lymphocytosis (HLH) and macrophage activation syndrome (MAS). The early diagnosis of NK cells defect responsible for the loss of the protective abilities is crucial for the prevention of life-threatening complications and implementation of necessary treatment.

Role of Natural Killer Cell Activity in the Pathogenesis of Endometriosis

Natural Killer (NK) cells are cytotoxic effector lymphocytes with the ability to lyse target cells in a major histocompatibility complex (MHC) class Ι-independent manner and without the need for prior antigen exposure. Data strongly suggested that NK cells play an important role in human reproduction and disturbance in their function can favor development of the gynecological disorders. In our study the role of NK cells in pathogenesis of endometriosis is reviewed and summarized from available literature. Endometriosis is related to a defect of NK cell cytotoxicity function in the ability to eliminate endometrial cells in ectopic sites. Alternations of the innate immunity mediated by NK cells may promote impairments or disrupt functions of adaptive immunity, which can contribute to development and progression of endometriosis and infertility associated with endometriosis. Aberrant immune responses by NK cells in affected women may represent risk factors for endometriosis and the repaired function can be a new treatment target of the affected women.

Natural killer cell in IgA nephropathy

Summary: Some studies have suggested that the cytotoxicity of the natural killer (NK) cell is inversely proportional to the expression of class I major histocompatibility complex (MHC) antigens on target cells. the increased activity of the NK cell in IgA nephropathy has been studied previously, however, little is known about the NK cell function in IgA nephropathy. We examined the cytotoxicity of NK cells in IgA nephropathy and investigated the change in class I MHC antigen expression on K562 cells treated with peripheral blood mononuclear cells (PBMC) culture supernatant of patients with IgA nephropathy, and its relation to K562 cell susceptibility to cytotoxicity of NK cells obtained from a normal healthy volunteer. We studied 10 IgA nephropathy patients (three males, seven females) and 10 age and sex matched healthy controls. the 10 IgA nephropathy patients had proteinuria (<100mg/dL) and microscopic haematuria. Their serum IgA levels in study patients were higher than those in healthy controls (292.2 ± 91.8 mg/dL vs 205.4 ± 43.4 mg/dL; P=0.014; mean age 37 years, range 19‐47 years). the cytotoxicity of NK cells was assayed by chromium‐release method. K562 cells were treated with PBMC culture supernatant of either patients or controls for 72 h. Part of the treated K562 cells were used to measure their susceptibility to cytotoxicity of NK cells from the healthy volunteer and the remainder were used to measure the MHC class I expression. Major histocompatibility complex class I expression was assayed using FAC Scan. Cytokines such as interleukin (IL)2, IL12, interferon‐γ (IFN‐γ), tumour necrosis factor‐α (TNF‐α), and transforming growth factor‐β (TGF‐β) in serum and PBMC culture supernatant were measured by ELISA. the following results were obtained: (i) cytotoxic activity of the NK cells from IgA nephropathy on K562 cells was higher than that obtained from healthy controls; (ii) pre‐treatment of K562 cells with PBMC culture supernatant resulted in decreased susceptibility to lysis of activated NK cells; (iii) the expression of class I MHC antigens on K562 cells was upregulated by treatment with PBMC culture supernatant; (iv) target cell susceptibility to cytotoxicity of NK cells was inversely proportional to the expression of class 1 MHC antigens (r = ‐0.71, P= 0.002); and (v) the expression of class I MHC antigens on K562 cells treated with PBMC culture supernatant correlated with the levels of IFN‐γ (r = 0.88, P= 0.0001) and TNF‐α (r = 0.926, P= 0.0001) in PBMC culture supernatant. However, there are no differences in the results (ii)‐(v) between patients and healthy controls. We conclude that the serum IgA levels and NK cell cytotoxicity found in IgA nephropathy patients with proteinuria and haematuria are higher than those of controls. K562 cell susceptibility to cytotoxicity of activated NK cells is inversely proportional to the expression of class I MHC antigens; however, this phenomenon is unlikely to be specific to IgA nephropathy. Further studies are needed in order to determine the role of NK cells in pathogenesis of IgA nephropathy.