ABSTRACT
BACKGROUND: After undergoing heart transplantation and the subsequent compulsive immunosuppressive treatments, patients are at risk of rejection episodes, infectious complications or cancer development. Thus, it is probable that the various subsets of peripheral cytotoxic lymphocytes are modulated in such patients. This area of study can now be investigated by examining the numerous recently described natural killer (NK)-cell-related surface receptors. METHODS: A prospective cohort of 60 heart transplant recipients and 60 controls was studied. The partitioning of lymphocyte subsets, especially NK (CD3-/CD56+), T (CD3+/CD56-) and NKT-like (CD3+/CD56+) cells, was compared in both groups using multi-parametric flow cytometry. Moreover, expression of a series of seven NK-related receptors was compared on the three subsets defined by CD56 expression. RESULTS: A significant increase in NK-cell levels was observed in transplanted patients, as compared with controls, whereas T and NKT-like cells were in similar proportions in both groups. Two NK-related receptors showed significantly different levels of expression in heart transplant recipients: the cytotoxic effector, CD244, which was in a significantly increased proportion on T and NKT-like cells; and the activating receptor, CD161, which was expressed significantly less on NK and NKT-like cells, but more on T cells. CONCLUSIONS: These findings indicate that cytotoxic NK-related cells, increased in proportion, also display increased levels of activity-associated markers in heart transplant recipients. Viral infection or the immunosuppressive regimen could be responsible for the modulation of regulatory receptors on NK and NKT-like cells in heart transplant recipients.
Subject(s)
Heart Transplantation/immunology , Killer Cells, Natural/chemistry , Killer Cells, Natural/immunology , Receptors, Immunologic/analysis , T-Lymphocytes/chemistry , T-Lymphocytes/immunology , Adult , Aged , Aged, 80 and over , Antigens, CD/analysis , Antigens, Surface/analysis , CD3 Complex/analysis , CD56 Antigen/analysis , Case-Control Studies , Female , Graft Rejection/immunology , Graft Rejection/pathology , Heart Transplantation/pathology , Heart Transplantation/physiology , Humans , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Infections/immunology , Infections/pathology , Killer Cells, Natural/drug effects , Killer Cells, Natural/pathology , Lectins, C-Type/analysis , Lymphocyte Subsets/chemistry , Lymphocyte Subsets/drug effects , Lymphocyte Subsets/immunology , Lymphocyte Subsets/pathology , Male , Middle Aged , NK Cell Lectin-Like Receptor Subfamily B , Prospective Studies , Receptors, Immunologic/drug effects , Receptors, Immunologic/physiology , Receptors, Natural Killer Cell , Signaling Lymphocytic Activation Molecule Family , T-Lymphocytes/drug effects , T-Lymphocytes/pathologyABSTRACT
Patients with renal failure represent a population at risk for hepatitis B, since only 50 to 60% of them develop protective humoral responses after vaccination. As this could be due to an altered regulation of cellular immune responses, the objectives of the present study were to evaluate the proliferative abilities of lymphocytes from patients with chronic renal failure after stimulation in vitro with a mitogen (pokeweed mitogen [PWM]) or HBsAg. In order to differentiate between the immunodeficiency associated with renal failure and that due to immunosuppression posttransplantation, the same subjects were tested before and 4 months after kidney transplantation. The lymphoproliferation assay used was performed by flow cytometry, which is based on sequential analysis of the cell cycle and which allows analysis of cytokine production. Serologically, the group of 36 patients tested comprised 22% nonresponders, 30% poor responders, and 48% responders. Lymphocyte growth was observed for all patients after stimulation with PWM, indicating that these cells had the capacity to proliferate in vitro. The level of lymphoproliferation in response to PWM was significantly reduced after transplantation, yet both before and after transplantation, all serologic nonresponders developed cellular responses to at least two vaccines. No correlation between humoral and cellular responses was shown. Proliferating cells were lymphocytes, which mostly secreted interleukin 4 (IL-4) and IL-10 for the three serologic groups. This study suggests that even when repeated vaccination fails to induce significant antibody levels in patients with renal failure, specific HBs cellular responses develop, and these may prove to be efficient in protecting these patients against hepatitis B.
