ABSTRACT
BACKGROUND: Natural killer (NK) cells provide a first line of immune defence towards infections and tumours, and participate in atherosclerosis and pregnancy diseases, of which there is a higher incidence in uraemic patients. Still, their relative contribution to the immunodeficient state associated with renal failure is poorly documented. METHODS: A multivariate and comparative analysis of lymphocyte subsets in haemodialysed (HD) and undialysed (UD) uraemic patients in comparison to healthy donors (HC) is provided in this article. NK-mediated cytotoxicity, degranulation and interferon secretion were compared in HD and HC. RESULTS: Evaluation of NK cells in 210 HD patients concluded with a decrease in NK cell counts in comparison to HC. Multivariate analysis associated lowered NK cell counts in UD patients with decreased renal clearance and higher NK counts HD with male gender and age. The 32% NK cell count decrease observed in sex- and age-matched groups (n = 88) was associated with B- and CD8(+)T-lymphocyte defects. NK cell functions were similar in subgroups of HD and HC matched for NK cell counts. Longer dialysis duration was associated with improved NK cytototoxic activity. While the expression of receptors modulating NK cytotoxicity were not modified, expression of the activation markers CD69 and NKp44, CD94 and chemokine receptors CX3CR1 and CXCR4 was altered in HD. CONCLUSIONS: This study is the first to associate decrease in renal function with selective fading of NK cell number and identify haemodialysis duration as a factor influencing NK cell function. It further shows that lower cell counts rather than intrinsic NK cell dysfunction per se characterize immune disorders in HD.
Subject(s)
Glomerular Filtration Rate/physiology , Immunity, Cellular/immunology , Killer Cells, Natural/immunology , Renal Dialysis/methods , Uremia/immunology , Antigens, CD/biosynthesis , Antigens, CD/immunology , Antigens, CD19/immunology , Antigens, Differentiation, T-Lymphocyte/biosynthesis , Antigens, Differentiation, T-Lymphocyte/immunology , B-Lymphocytes/immunology , CD3 Complex/immunology , CD4 Antigens/immunology , CD8-Positive T-Lymphocytes/immunology , CX3C Chemokine Receptor 1 , Cytotoxicity Tests, Immunologic , Female , Flow Cytometry , Follow-Up Studies , Humans , Lectins, C-Type , Lymphocyte Activation , Lymphocyte Count , Lysosomal-Associated Membrane Protein 1/biosynthesis , Lysosomal-Associated Membrane Protein 1/immunology , Male , Middle Aged , Multivariate Analysis , NK Cell Lectin-Like Receptor Subfamily D/biosynthesis , NK Cell Lectin-Like Receptor Subfamily D/immunology , Natural Cytotoxicity Triggering Receptor 2 , Phenotype , Prognosis , Receptors, CXCR4/biosynthesis , Receptors, CXCR4/immunology , Receptors, Chemokine/biosynthesis , Receptors, Chemokine/immunology , Receptors, Immunologic/biosynthesis , Receptors, Immunologic/immunology , Uremia/physiopathology , Uremia/therapyABSTRACT
BACKGROUND: Recently introduced immunosuppressive drugs are more potent to control graft rejection, but current concerns are raised regarding their potential to increase long-term neoplastic and infectious complications. Considering the role of B, T, or natural killer (NK) lymphocyte in controlling alloreactive, anti-infectious, and antitumoral immune responses, we compared the impact of two immunosuppressive regimens on lymphocyte subsets one year following kidney transplant. METHODS: Multivariate regression analysis of variables affecting lymphocyte subset counts was retrospectively performed on 91 kidney-transplanted patients, analyzed before graft, at day 15 and 1-year postgraft. These patients were included in a randomized prospective open trial comparing tacrolimus/mycophenolate mofetil (FK/MMF) versus cyclosporine/azathioprine (CSA/Aza), both used in association with rabbit antithymocyte globulines (rATG) induction and prednisone. RESULTS: Fifteen days postgraft, severe T and NK lymphocyte depletion were observed in all patients, while B cell counts were selectively higher in the FK/MMF group as compared to before graft. One-year posttransplant, NK cell counts and NK cell cytotoxicity was significantly higher in patients receiving FK/MMF therapy, as compared to CSA/Aza. Cytomegalovirus (CMV) infection during the first year posttransplant was also associated to higher NK, CD8, and CD4CD8 T cell counts at month 12. CONCLUSIONS: In addition to its higher potential in preventing graft rejection, we show that after one year of transplant, FK/MMF better preserves NK innate immune effector cells and their cytotoxic potential. These data prompt to further evaluate the role of NK cells in relation to antiviral and tumoral surveillance of transplanted patients, which are common complications of long-term immunosuppression.