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

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

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 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

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 ; Antigens, Neoplasm ; biosynthesis ; genetics ; immunology ; Apoptosis ; physiology ; Breast Neoplasms ; immunology ; metabolism ; CD3 Complex ; immunology ; Female ; Humans ; Killer Cells, Natural ; pathology ; Neoplasms ; immunology ; metabolism ; Receptors, Antigen, T-Cell ; immunology ; Stomach Neoplasms ; immunology ; metabolism ; Uterine Cervical Neoplasms ; immunology ; metabolism

AIMTo increase the cognition of cerebellar functions and the knowledge of neuroimmunology, the effect of cerebellar interposed nuclei (IN), one of three deep nuclei in cerebellum, on lymphocyte function was investigated.

METHODSKainic acid (KA) was microinjected into bilateral IN for lesions of neuronal bodies in the IN. Control rats was microinjected with saline into their IN. On days 8, 16 and 32 following the IN lesions, the lymphocyte number in the peripheral blood was measured by blood corpuscle counter. Meanwhile, lymphocyte proliferation induced by concanavalin A (Con A), cytotoxicity of natural killer (NK) cells against YAC-1 cells, and anti-SRBC IgM antibody in the serum were examined respectively by methyl-thiazole-tetrazolium (MTT) assay, flow cytometry and ELISA assay.

RESULTSThe lymphocyte number in the peripheral blood was significantly reduced on days 8, 16 and 32 following the effective lesions of the bilateral IN in comparison with that of control. The Con A-induced lymphocyte proliferation, the NK cell cytotoxicity to YAC-1 cells, and the titer of anti-SRBC IgM antibody in the serum, were all significantly attenuated on days 8, 16 and 32 following the effective lesions of the bilateral IN in comparison with those of control. There were not remarkable differences between the days 8, 16 and 32 in the decreased lymphocyte number and functions induced by the lesions of the bilateral IN.

CONCLUSIONEffective lesions of the cerebellar bilateral IN of rats cause an inhibition in lymphocyte number and functions of T, B and NK cells, strongly showing that the cerebellar IN can modulate lymphocyte functions.

Animals ; Cerebellar Nuclei ; immunology ; physiology ; Cerebellum ; immunology ; physiology ; Female ; Kainic Acid ; Killer Cells, Natural ; immunology ; Lymphocyte Count ; Lymphocytes ; immunology ; Male ; Microinjections ; Neuroimmunomodulation ; immunology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The immunomodulatory and antitumor effects of lactic acid bacteria (LABs) were investigated. Cytoplasmic fraction of Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium longum were tested for the antiproliferative activity in vitro to SNUC2A, SNU1, NIH/3T3 and Jurkat cell lines by crystal violet assay. All cytoplasmic fraction suppressed proliferation of tumor cells, though L. casei and B. longum were more effective. From these results, cytoplasmic fraction of L. casei and B. longum with Y400 as a control were administered as dietary supplements to Balb/c mice for 2, and 4 consecutive wks. Administration for 4 wks enhanced the number of total T cells, NK cells and MHC class II+ cells, and CD4-CD8+ T cells in flow cytometry analysis. To determine of antitumor activity of LABs preparation in vivo, F9 teratocarcinoma cells were inoculated on mice at 14th day. Body weight was decreased with increased survival rate in all groups with the cytoplasm of LABs. Our results showed that cytoplasmic fraction of LABs had direct antiproliferative effects on tumor cell lines in vitro, effects on immune cells in vivo, and antitumor effects on tumor-bearing mice with prolonged survival periods.
3T3 Cells ; Animals ; *Bifidobacterium ; Body Weight ; Cell Division/physiology ; Cytotoxicity, Immunologic ; Flow Cytometry ; Humans ; Immunophenotyping ; Jurkat Cells ; Killer Cells, Natural/immunology ; *Lactobacillus casei ; Male ; Mice ; Mice, Inbred BALB C ; Neoplasms, Experimental/immunology/*therapy ; Probiotics/*pharmacology ; Survival Analysis ; T-Lymphocytes/immunology

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