ABSTRACT
BACKGROUND: Distinct functional subsets of natural killer cells potentially contribute to the pathology of inflammatory bowel disease (IBD). AIM: To report the phenotypic and functional characteristics of natural killer cells in blood and lamina propria of IBD patients, and the effect of azathioprine. METHODS: Natural killer cells from blood and lamina propria of healthy controls or patients with Crohn's disease, or ulcerative colitis were studied by flow cytometry. Activation, cytokine production, proliferation and apoptosis of natural killer cell subsets were studied in vitro. RESULTS: CD16(+) natural killer cells are increased in frequency in the lamina propria comparing Crohn's disease or ulcerative colitis with healthy controls. Azathioprine therapy was associated with a reduction in total natural killer cells in blood and lamina propria, preferentially of the CD16(+) subset. Azathioprine therapy did not impair natural killer degranulation, but reduced natural and cytokine-activated cytotoxicity and interferon-gamma (IFN-γ) production. Culture of resting peripheral blood mononuclear cells with azathioprine resulted in loss of natural killer cells and inhibition of activation and IFN-γ production. Azathioprine preferentially inhibited proliferation of CD16(+) natural killer cells and induced apoptosis in resting but not in pre-activated natural killer cells. CONCLUSIONS: Natural killer cells with cytolytic potential are enriched in the colonic lamina propria of individuals with IBD. Azathioprine is associated with a reduction in these cells and a normalization of natural killer cell populations.
Subject(s)
Azathioprine/therapeutic use , Colon/immunology , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Killer Cells, Natural/drug effects , Mucous Membrane/immunology , Adult , Aged , Case-Control Studies , Colon/pathology , Cross-Sectional Studies , Female , Humans , Inflammatory Bowel Diseases/blood , Inflammatory Bowel Diseases/immunology , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Male , Middle Aged , Mucous Membrane/pathology , Severity of Illness Index , Treatment Outcome , Young AdultABSTRACT
Kaposi's sarcoma (KS) is an AIDS-defining condition in individuals with human immunodeficiency virus type 1 infection. We investigated the phenotype and function of the NKG2C+ NK cell population in individuals with AIDS and Kaposi's sarcoma. The staging of AIDS KS patients according to the AIDS Clinical Trial Group criteria revealed that patients with the S1 disease stage have a significantly higher proportion of NKG2C+ cells than those with the S0 disease stage. NKG2C+ cells from S1-stage patients are highly enriched for the expression of KIR3DL1, are depleted of NKp46, and respond poorly to major histocompatibility complex class I-positive target cells. These data demonstrate a link between NK cell phenotype and function and disease prognosis in AIDS.
Subject(s)
Acquired Immunodeficiency Syndrome/complications , Killer Cells, Natural/immunology , Receptors, Immunologic/metabolism , Sarcoma, Kaposi/immunology , Acquired Immunodeficiency Syndrome/immunology , Humans , NK Cell Lectin-Like Receptor Subfamily C , Neoplasm Staging , Phenotype , Receptors, Natural Killer Cell , Sarcoma, Kaposi/complicationsABSTRACT
Efficacious protection for future generations from HIV-1 infection through the development of prophylactic vaccines is the best hope for the millions of individuals living with the threat of HIV-1 infection. Advances in the development of non-curative chemotherapy for those already infected have changed the course of the epidemic for those with access to the drugs. However in the ten years since the advent of highly active anti-retroviral therapy, the expectancy of curative chemotherapy has been quashed, and the constant need for a next generation of drugs is evident. As our understanding of HIV-1 pathogenesis increases, it is becoming apparent that novel approaches and strategies will be required to halt the global progression of HIV-1. Immune-based therapies are being considered in the context of effective antiretroviral therapy. Such immune-based therapy must allow the induction or regeneration of HIV-1-specific T-cell responses with the potential to control viremia and purge viral reservoirs. Studies of therapy substitution, treatment interruption, therapeutic vaccines and/or cytokines and/or hormones have been carried out and are briefly summarised in this review.
