A depressed level of natural killer (NK) activity is one of the various immunologic abnormalities in human immunodeficiency virus (HIV) infection. Interleukin-15 (IL-15), an immunotherapeutic candidate in HIV infection, increases NK activity and induces the excretion of CC-chemokines from divergent immune cells, but the mechanisms of NK activity enhancement by IL-15 stimulation is not clearly established in HIV infection. This study examined whether CC-chemokines, which are known to increase NK activity, are secreted adequately in HIV-infected individuals, and also investigated whether P-glycoprotein is involved in NK activity enhancement after IL-15 administration. NK activity increased with IL-15 stimulation in NK cells of HIV-infected individuals, as it does in normal NK cells. IL-15 stimulates NK cells to secrete CC-chemokines, such as, macrophage inflammatory protein-1alpha (MIP-1alpha), macrophage chemotactic protein-1alpha (MCP-1alpha) and regulated upon activation, normal T cells expressed and secreted (RANTES) in both HIV-infected individuals and controls with no significant difference. P-glycoprotein expression and function is decreased in HIV-infected individuals and restored only in NK cells of HIV-infected individuals after IL-15 stimulation. P-glycoprotein may play a role in the mechanism of increased NK cell activity in HIV-infected individuals after IL-15 stimulation.
HIV Infections/physiopathology* ; HIV Infections/pathology ; Human ; Interleukin-15/pharmacology* ; Killer Cells, Natural/physiology* ; Killer Cells, Natural/drug effects* ; P-Glycoprotein/physiology* ; Recombinant Proteins/pharmacology

Human cytomegalovirus (HCMV) is an ubiquitous pathogen that infects a majority of the world's population. The virus can establish lifelong infection once the human body is infected by HCMV and virus can be reactivated from a latent state in immune suppressed individuals. HCMV has developed several strategies to evade host immune surveillance after millions of years of co-evolution with mankind. One of the classical tricks is encoding homologous to human immune factors or stealing host cellular genes that have significant functions in immune system. Virus encoded immune modulators which participate in regulating the major histocompatibility complex, cellular immunity, humoral immunity, cytokines and chemokines are supposed to play a significant role in the pathogenesis of HCMV. Evaluation of "mutually assured survival" relationship between virus and host provides important insights into viral immunopathogenesis and study of viral immunomodulatory proteins might help us to uncover new human genes that control immunity.
Animals ; Chemokines ; physiology ; Cytokines ; physiology ; Cytomegalovirus ; pathogenicity ; Cytomegalovirus Infections ; immunology ; Game Theory ; Humans ; Immunity, Humoral ; Killer Cells, Natural ; immunology

Interleukin-21 (IL-21) is a new member of the interleukin-2 family. It is mainly synthesized and secreted by the activated of CD4(+) T cells and natural killer T cells. IL-21 receptor (IL-21R) is mainly expressed in T cells, B cells, and natural killer (NK) cells. After binding to its receptor, IL-21 can regulate the activation and proliferation of T cells, B cells, and NK cells through activating JAKs-STATs signaling pathways. As a new immunoregulatory factor, IL-21 and its receptor play important roles in the development and progression of various autoimmune diseases. Regulation of the expression levels of IL-21 and IL-21R and blocking of their signal transduction pathways with blockers may be new treatment options for autoimmune diseases.
Animals ; Autoimmune Diseases ; etiology ; immunology ; Dendritic Cells ; immunology ; Humans ; Interleukins ; physiology ; Killer Cells, Natural ; immunology ; Lymphocytes ; immunology ; Receptors, Interleukin-21 ; physiology

OBJECTIVETo explore the role of natural killer T (NK T) cells in the pathogenesis of Graves' disease.

METHODSNK T cell deficient mice and wild BALB/c mice were immunized with cells expressing TSH receptor once every two weeks 6 times. Two weeks after the final immunization, the mice were killed and serum thyroxine levels, anti-TSH receptor antibodies and thyroid pathological changes were examined.

RESULTSThe mean levels of TT(4) and TRAb in the immunized NK T cell deficient group were slightly elevated but significantly different from those of the non-immunized control group, while comparable to those in the immunized wild group. There were no significant changes of the activity levels of TSAb or TSBAb in the immunized NK T cell deficient mice compared to those in immunized wild control mice. Thyroids from immunized NK T cell deficient mice showed mild hypertrophy of some follicles as compared with non-immunized control mice. This change was comparable to immunized wild control mice.

CONCLUSIONNK T cells may not be involved in the pathogenesis of Graves' disease.

Animals ; CHO Cells ; Cricetinae ; Female ; Graves Disease ; etiology ; immunology ; Immunization ; Killer Cells, Natural ; physiology ; Mice ; Mice, Inbred BALB C ; Receptors, Thyrotropin ; immunology ; Thyroid Gland ; pathology

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs). Circulating MAIT and NKT cell levels in the peripheral blood were measured by flow cytometry. The severity of injury was categorised according to the scoring systems, such as Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, and Injury Severity Score (ISS). Circulating MAIT and NKT cell numbers were significantly lower in multiple trauma patients than in HCs. Linear regression analysis showed that circulating MAIT cell numbers were significantly correlated with age, APACHE II, SAPS II, ISS category, hemoglobin, and platelet count. NKT cell numbers in the peripheral blood were found to be significantly correlated with APACHE II, SAPS II, and ISS category. This study shows numerical deficiencies of circulating MAIT cells and NKT cells in multiple trauma. In addition, these invariant T cell deficiencies were found to be associated with disease severity. These findings provide important information for predicting the prognosis of multiple trauma.
APACHE ; Autoimmunity ; Cell Count ; Cohort Studies ; Communicable Diseases ; Flow Cytometry ; Humans ; Injury Severity Score ; Linear Models ; Multiple Trauma* ; Natural Killer T-Cells* ; Physiology ; Platelet Count ; Prognosis ; T-Lymphocytes*

The profound graft-versus-leukemia (GVL) effect presented after allogeneic hematopoietic cell transplantation (allo-HSCT) has been evidenced. In contrast to T cell mediated GVL, natural killer (NK) cells recognize target cells and introduce GVL effect by using an integration of activating and inhibitory receptors. This review has summarized current literatures from 2001 - 2003 on human killer cell immunoglobulin receptors (KIR) and other NK cell receptors involved in recognition of tumor targets and the polymorphism of KIR genes of donor/recipient pairs of related and unrelated Allo-HSCT. KIR epitope mismatch may facilitate engraftment and reduce leukemia relapse post transplant by mediating lysis of recipient's cells and introducing GVL effect under the condition of KIR epitope mismatch. Clinical roles of KIR in Allo-HSCT and immunotherapy are discussed. Technologic approach in allogeneic reactive NK cells introduction, identification and selection in vitro, development of inhibitory receptor blockade as well as up-regulation of activating NK cells may significantly enhance GVL immune response. Further investigation on the regulation of KIR inhibitory receptors enables to design novel strategy in cancer immunotherapy over the forthcoming decade.
Graft vs Host Disease ; immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune Tolerance ; Killer Cells, Natural ; immunology ; Major Histocompatibility Complex ; Receptors, Immunologic ; chemistry ; genetics ; physiology ; Receptors, KIR ; Transplantation, Homologous

Animals ; Cytotoxicity, Immunologic ; Down-Regulation ; Humans ; Influenza A Virus, H1N1 Subtype ; immunology ; physiology ; Influenza, Human ; immunology ; therapy ; virology ; Killer Cells, Natural ; immunology ; virology

Research on innate lymphoid cells (ILC) has recently been a fast paced topic of immunological research. As ILCs are able to produce signature Th cytokine, ILCs have garnered considerable attention and have been described to represent the innate counterpart of the CD4 T helper (Th) cells. The development and function of ILCs are precisely regulated by a network of crucial transcription factors, which are also involved in the development or differentiation of conventional natural killer (cNK) cells and T cells. In this review, we will summarize the key transcriptional regulators and their functions through each phases of ILC development. With the phase of ILC lineage commitment, we will focus in particular on the roles of the transcription regulators Id2 and GATA-3, which in collaboration with other transcriptional factors, are critically involved in the generation of ILC fate determined progenitors. Once an ILC lineage has been established, several other transcription factors are required for the specification and functional regulation of distinct mature ILC subsets. Thus, a comprehensive understanding of the interactions and regulatory mechanisms mediated by these transcription factors will help us to further understand how ILCs exert their helper-like functions and bridge the innate and adaptive immunity.
Animals ; GATA3 Transcription Factor ; immunology ; Humans ; Immunity, Innate ; physiology ; Inhibitor of Differentiation Protein 2 ; immunology ; Killer Cells, Natural ; immunology ; T-Lymphocytes, Helper-Inducer ; immunology

BACKGROUND/AIMS: This study aimed to detect the expression of natural killer (NK) cell receptor natural killer group 2D (NKG2D) in the peripheral blood of patients with primary hepatocellular carcinoma and to discuss the correlation between NK cell cytotoxicity and liver function. METHODS: The number of NK cells and the expression of NK cell receptor NKG2D in peripheral blood were determined by flow cytometry in patients with primary hepatocellular carcinoma, hepatitis B cirrhosis, chronic hepatitis B, and healthy controls. RESULTS: When compared with patients in the healthy and the chronic hepatitis B groups, the primary hepatocellular carcinoma group showed significant decreases in all parameters, including the cytotoxicity of NK cells on K562 cells, expression rate of NKG2D in NK cells, number of NKG2D+ NK cells, expression level of NKG2D, and number of NK cells (p<0.05). The activity of NK cells showed a positive correlation, whereas the Child-Pugh scores in the primary hepatocellular carcinoma and the hepatitis B cirrhosis groups showed a negative correlation with all parameters detected above. CONCLUSIONS: The decrease of NK cell activity in patients with primary hepatocellular carcinoma is closely related to their lower expression of NKG2D. Liver function affects the expression of NKG2D and the activity of NK cells.
Carcinoma, Hepatocellular/*physiopathology ; Case-Control Studies ; Female ; Humans ; K562 Cells ; Killer Cells, Natural/*physiology ; Liver Neoplasms/*physiopathology ; Lymphocyte Subsets/physiology ; Lymphopenia/physiopathology ; Male ; Middle Aged ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; T-Lymphocytes, Cytotoxic/physiology

OBJECTIVETo explore the effects of electroacupuncture on exercise-induced immunosuppression in rats and its mechanism.

METHODSSports immunosuppressive model was established successfully by the rats were conducted high intensity swimming training 150 min/day, 6 days/wk for 8 weeks in this study. Forty-three SD rats were randomly divided into a control group (group A, n = 10), a high intensity swimming training group (group B, n = 17), and a high intensity plus electroacupuncture group (group C, n = 16). Group A did not receive any intervention. Group B was conducted 150 min/day, 6 days/wk swimming training for 8 weeks. Group C was treated with electroacupuncture at "Baihui" (GV 20), "Guanyuan" (CV 4) and "Zusanli" (ST 36) after every exercise-time from the second week, once each day for 7 weeks. The changes of the rats' weight, gamma-interferon (gamma-IFN), interleukin-2 (IL-2), solubility IL-2 receptor (SIL-2R) and nature killer cell (NKC) were detected.

RESULTS(1) Compared with group A, gamma-IFN and IL-2 in group B were significantly decreased (P < 0.01, P < 0.05), and NKC in group C was significantly increased (P < 0.01). Meanwhile, gamma-IFN and NKC in group C were both significantly higher than that in group B (P < 0.05, P < 0.01). (2) Compared with group A, the weight of the rats in group B and group C were significantly decreased (both P < 0.01), but SIL-2R in group B was significantly increased (P < 0.05). The weight of the rats in group C was significantly higher than that in group B (P < 0.05) and SIL-2R in group C was significantly lower than that in group B (P < 0.01).

CONCLUSIONLasting gravis exercise stress does decrease the immune function in rats and is even inhibited significantly, but electroacupuncture can up-regulate the exercise-induced immunosuppression.

Animals ; Electroacupuncture ; Interferon-gamma ; blood ; physiology ; Interleukin-2 ; blood ; physiology ; Killer Cells, Natural ; immunology ; Male ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Receptors, Interleukin-2 ; blood ; physiology ; Stress, Physiological ; immunology