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

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

Epstein-Barr virus, a ubiquitous human herpesvirus, can induce both lytic and latent infections that result in a variety of human diseases, including lymphoproliferative disorders. The oncogenic potential of Epstein-Barr virus is related to its ability to infect and transform B lymphocytes into continuously proliferating lymphoblastoid cells. However, Epstein-Barr virus has also been implicated in the development of T/natural killer cell lymphoproliferative diseases. Epstein-Barr virus encodes a series of products that mimic several growth, transcription and anti-apoptotic factors, thus usurping control of pathways that regulate diverse homeostatic cellular functions and the microenvironment. However, the exact mechanism by which Epstein-Barr virus promotes oncogenesis and inflammatory lesion development remains unclear. Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases often have overlapping clinical symptoms as well as histologic and immunophenotypic features because both lymphoid cell types derive from a common precursor. Accurate classification of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases is a prerequisite for appropriate clinical management. Currently, the treatment of most T/natural killer cell lymphoproliferative diseases is less than satisfactory. Novel and targeted therapies are strongly required to satisfy clinical demands. This review describes our current knowledge of the genetics, oncogenesis, biology, diagnosis and treatment of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases.
Cell Transformation, Viral ; Epstein-Barr Virus Infections/*complications ; Herpesvirus 4, Human/*physiology ; Humans ; Killer Cells, Natural/immunology/metabolism/*pathology/*virology ; Lymphoproliferative Disorders/diagnosis/*etiology/therapy ; T-Lymphocytes/immunology/metabolism/*pathology/*virology

The development of highly immunodeficient mouse strains has allowed the reconstitution of functional human immune system components in mice. New-generation humanized mice generated in this manner have been extensively used for modeling viral infections that are exclusively human tropic. Epstein-Barr virus (EBV)-infected humanized mice reproduce cardinal features of EBV-associated B-cell lymphoproliferative disease and EBV-associated hemophagocytic lymphohistiocytosis (HLH). Erosive arthritis morphologically resembling rheumatoid arthritis (RA) has also been recapitulated in these mice. Low-dose EBV infection of humanized mice results in asymptomatic, persistent infection. Innate immune responses involving natural killer cells, EBV-specific adaptive T-cell responses restricted by human major histocompatibility and EBV-specific antibody responses are also elicited in humanized mice. EBV-associated T-/natural killer cell lymphoproliferative disease, by contrast, can be reproduced in a distinct mouse xenograft model. In this review, recent findings on the recapitulation of human EBV infection and pathogenesis in these mouse models, as well as their application to preclinical studies of experimental anti-EBV therapies, are described.
Animals ; Disease Models, Animal ; Epstein-Barr Virus Infections/complications/immunology/*virology ; Herpesvirus 4, Human/*physiology ; Heterografts ; Humans ; Killer Cells, Natural/pathology/virology ; Lymphoproliferative Disorders/etiology ; Mice ; Mice, SCID ; T-Lymphocytes/pathology/virology

Killer cell immunoglobulin-like receptors (KIRs) which are mainly expressed on natural killer (NK) cells are implicated in many virus infections. However, it is unclear whether or not KIRs are associated with susceptibility to Epstein-Barr virus (EBV) infection related diseases. Therefore, the purpose of our study was to investigate possible correlation between polymorphisms of KIR genes and infectious mononucleosis (IM)/EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). The polymorphisms of KIR genes were detected by polymerase chain reaction with sequence-specific primers (PCR-SSP). The results would contribute to clarify the association of KIRs with EBV induced diseases, and provide new insights into the role of NK cells and innate immune response against viral infections and/or subsequent progression.
Case-Control Studies ; Child ; Child, Preschool ; China ; Disease Progression ; Female ; Herpesvirus 4, Human ; physiology ; Humans ; Immunity, Innate ; Infectious Mononucleosis ; genetics ; immunology ; virology ; Killer Cells, Natural ; immunology ; metabolism ; Lymphohistiocytosis, Hemophagocytic ; genetics ; immunology ; virology ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Receptors, KIR ; genetics ; metabolism

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

OBJECTIVETo review the mechanisms by which HIV evades different components of the host immune system.

DATA SOURCESThis review is based on data obtained from published articles from 1991 to 2012. To perform the PubMed literature search, the following key words were input: HIV and immune evasion.

STUDY SELECTIONArticles containing information related to HIV immune evasion were selected.

RESULTSAlthough HIV is able to induce vigorous antiviral immune responses, viral replication cannot be fully controlled, and neither pre-existing infected cells nor latent HIV infection can be completely eradicated. Like many other enveloped viruses, HIV can escape recognition by the innate and adaptive immune systems. Recent findings have demonstrated that HIV can also successfully evade host restriction factors, the components of intrinsic immune system, such as APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G), TRIM5α (tripartite motif 5-α), tetherin, and SAMHD1 (SAM-domain HD-domain containing protein).

CONCLUSIONSHIV immune evasion plays an important role in HIV pathogenesis. Fully understanding the tactics deployed by HIV to evade various components of the host immune systems will allow for the development of novel strategies aimed toward the prevention and cure of HIV/AIDS.

APOBEC-3G Deaminase ; Adaptive Immunity ; Antibodies, Neutralizing ; immunology ; Antigens, CD ; physiology ; Carrier Proteins ; physiology ; Complement System Proteins ; immunology ; Cytidine Deaminase ; physiology ; GPI-Linked Proteins ; physiology ; HIV-1 ; immunology ; Humans ; Immune Evasion ; Killer Cells, Natural ; immunology ; Monomeric GTP-Binding Proteins ; physiology ; SAM Domain and HD Domain-Containing Protein 1

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

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

OBJECTIVETo explore the dynamic effects of Yinqiao detoxifcation oral liquid (YQD) on NK cell lysis in spleen and serum concentration of IFN-gamma in SCID mouse infected by influenza A virus FM1.

METHODThe mice were divided into six different groups randomly. Except normal control, other mice were intranasally instilled with 15 TCID of virus. Three dosage groups of YQD (5.0, 10.0, 20.0 g x kg(-1)) were respectively fed with YQD. Positive control group was administrated orally with 0.07 g x kg(-1) of ribavirin. Normal control and model group were fed with physiological saline. After 1, 3, 5 and 7 days' infection, spleens and serum were collected. Then the NK cell lysis was detected by LDH release kit and the concentration of IFN-gamma was examined by ELISA assay.

RESULTContents of IFN-gamma reached to peak value on the 3th day and until the 5th day. Later, the level of IFN-gamma returned to normal level. The variation tendency of activity of NK cell in spleen was according with that of IFN-gamma. But it reached the maximum value until the 5th day. The activity of NK cell lysis in three groups of YQD was well above that i n model group. In addition, therapeutic action of both 10.0 g x kg(-1) and 20.0 g x kg(-1) of YQD treatment groups was better than that of 5.0 g x kg(-1).

CONCLUSIONThe data showed that serum concentration of IFN-gamma and NK cell lysis were improved by YQD at different time, which was demonstrated YQD could perform well in immune system.

Animals ; Cell Survival ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Humans ; Influenza, Human ; blood ; drug therapy ; immunology ; physiopathology ; Influenzavirus A ; physiology ; Interferon-gamma ; blood ; Killer Cells, Natural ; drug effects ; physiology ; Mice ; Mice, SCID ; Random Allocation ; Spleen ; immunology ; physiopathology