ABSTRACT
Background: Highly active antiretroviral therapy (HAART) in HIV/AIDS infection induces an important reduction of the viral load (VL) and an immune system reconstitution. CD4+ T lymphocyte count is the immunological measurement commonly used for the follow up of HIV/AIDS patients. Aim: To study prospectively the restoration of the innate immune system in patients with HIV/AIDS infection during their first year on HAART. Patients and Methods: 25 naive HIV/AIDS patients, from San José Hospital and University of Chile Clinical Hospital, Santiago, Chile, were studied between years 2002-2003. Every 4 months after HAART initiation, CD3+, CD4+, CD8+ T lymphocytes and CD16/56+ natural killer (NK) cells were quantified by flow cytometry. NK cell cytotoxicity was measured using radioactive chrome liberation (Cr51). Tumor necrosis factor alpha (TNF-a) and interleukin-10 (IL-10) were measured in peripheral blood mononuclear cells and viral load was determined using Amplicor HIV-1 from Roche Diagnostics Systems. Results: Thirteen of the 25 patients continued in the study. They were all males, average age 35 years old (23-50). At baseline average CD4+ count was 146 cells/µL (31-362) and average viral load was 82.000 copies/mL (4.000-290.000). A raise in CD3+, CD4+, CD8+, and CD16/56 cells was noted at months 9-12 of therapy. Viral load became undetectable in the same period. NK cell function was decreased at the beginning of the therapy (1-4 months), reaching its highest values at months 9-12. There was no significant change in IL-10. TNF-a increased in six patients during the study. Conclusions: In this group of patients, innate immunity was restored during HAART. These results should be confirmed in studies with a longer follow up period and also measuring cytokines such as MIP-1a, MIP-1ß and RANTES.
Subject(s)
Adult , Humans , Male , Middle Aged , HIV-1 , Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , HIV Infections/immunology , Immunity, Innate , HIV-1 , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/immunology , Follow-Up Studies , HIV Protease Inhibitors/therapeutic use , /blood , Killer Cells, Natural/radiation effects , Prospective Studies , Reverse Transcriptase Inhibitors/therapeutic use , Time Factors , Tumor Necrosis Factor-alpha/blood , Viral LoadABSTRACT
Natural killer (NK) cells form a unique third group of lymphocytes that differs from T and B cells in surface phenotype, target cell recognition and function. NK cells have two relevant functions, related to the innate immune response against pathogens microorganisms. One is cytotoxicity, mediated by the recognition and lysis of target cells such as virus and bacteria infected-cells. The second NK cell function is to produce cytokines, mainly IFN-g, that can modulate innate and specific immune responses. Cytotoxicity and cytokine secretion contribute to host resistance against microorganisms and both functions are significantly altered in infectious diseases
Subject(s)
Humans , Communicable Diseases/immunology , Lymphocyte Subsets/immunology , Killer Cells, Natural/immunology , Cytokines , Immune System/immunology , Killer Cells, Natural/physiology , Cytotoxicity, Immunologic/immunology , Antibody Formation/immunology , Shock, Septic/immunologyABSTRACT
Las células Natural Killer (cél NK), linfocitos efectores de actividad citolítica natural, son críticas en la defensa antiinfecciosa. En la infección por VIH-I se ha descrito una disminución de la actividad citolítica NK; sin embargo, se desconocen los mecanismos involucrados, por lo que el objetivo de este trabajo fue estudiar la ACNK y la acción in vitro de inmunomoduladores para intentar explicar esta deficiencia. Se analizaron 20 individuos infectados por VIH-I (10 asintomáticos y 10 con SIDA) y 30 individuos seronegativos como controles. La ACNK se determinó utilizando cél K-562 radiomarcadas con 51-Cr (cromato de sodio) como cél blanco y cél mononucleares periféricas como cél efectoras, expresándose los resultados como por ciento de Lisis específica. En cultivos in vitro, se analizó el efecto de inmunomoduladores sobre la ACNK: interleuquina-2 (IL-2, 25 U/mL), interferon-alfa (IFN-a, 500 U/mL) y la acción conjunta de ionófor de calcio A23187 (lo, 10.0 uM) más un éster de forbol (TPA, 250 ng/mL)(Io+TPA). El análisis fenotípico, CD 16+/56+ se efectuó por citometría de flujo con Ac monoclonales fluorescentes (Becton Dickinson)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Killer Cells, Natural/immunology , HIV Infections/immunology , HIV-1/pathogenicity , Adjuvants, Immunologic/analysis , Case-Control Studies , Flow Cytometry/methods , Cytotoxicity, Immunologic/physiologyABSTRACT
Blood samples were obtained from 42 medical students during a period of moderate academic stress, immediately before a final examination and after their summer vacations. T lymphocyte proliferation in response to 5, 10 and 20 mg/ml phytohemagglutinin was measured by the incorporation of 3H-thymidine, and plasma cortisol was measured by RIA. Results: T lymphocyte stimulation index in response to all phytohemagglutinin concentrations was significatively lower in the period before examination than in the other two periods.There were no differences in the index between the period of moderate stress and after summer vacations. Plasma cortisol levels were 15.6 ñ 4.3, 18.6 ñ 5.8 and 16.7 ñ 5.1 mg/dl during the periods of moderate stress, before the examination and after vacations, respectively (p < 0.05 for the difference between examination and the other two periods). Conclusions: There is a decrease in lymphocyte proliferation and an increase in cortisol levels during a period of acute academic stress in medical students, suggesting that, the exposure of healthy subjects to common stress ful stimuli, may affect their immunocompetance
Subject(s)
Humans , Male , Female , Adult , T-Lymphocytes/immunology , Immune System/physiopathology , Stress, Psychological/immunology , Students, Medical/psychology , Hydrocortisone/blood , Immunocompetence/physiology , Lymphoproliferative Disorders/diagnosisABSTRACT
Natural killer cytolitic activity, the basis of cancer immunotherapy that uses cytolytic cells, may be impaired in cancer. The aim of this work was to study in vitro the natural killer cytolitic activity and its response to the immunomodulators interleukin-2 interferon and phytohemagglutinin stimulated lymphocyte proliferation in a group of 9 patients with renal cell cancer and 6 with prostatic cancer. The results were compared with those of 20 normal volunteers. Twelve patients were operated and were studied twice 48 h and 14 days after surgery. Natural killer cytolitic activity was significantly lower in renal cell and prostatic cancer patients than controls (3.3 ñ 1.6, 4.9 ñ 2.2 and 20.6 ñ 3.7 per cent of specific lysis respectively). This activity was not modified in cancer patients by interleukin-2 50 Ul/ml or interferon 3000 Ul/ml and did not differ in the two postoperative pèriods. Phytohemagglutinin stimulated lymphocyte proliferation was also lower in cancer patients, compared to controls (stimulation index of 18 ñ 3 and 26.5 ñ 5 respectively). It is concluded that these patients have a low immunological level and this study is the first step towards an immunological characterization of cancer patients that are candidate to adoptive immunotherapy
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Prostatic Neoplasms/immunology , Kidney Neoplasms/immunology , Killer Cells, Natural/physiology , Phytohemagglutinins/immunology , Cell Separation/methods , Cytotoxicity Tests, Immunologic/methodsABSTRACT
It is well fnown that an immunosuppresive rsponse occuts after acute trauma. Some cellular mediators participate in the pathogenesis of septic shock. However, the exact role of the lymphocyte subsets and natural killer (NK) activity in this condition is not clear. We studied NK cytolytic activity through a 51Cr liberation assay using K-562 target cells in 20 patients with initial septic shock (10 men and 10 females, mean age 41 years old). Lymphocyte subsets CD3 (T3), CD4 (T4), CD8 (T8), CD16 (Leu-11) and CD56 (Leu-19) wetre also studied by indirect immunofluorescence. Compared to tesults obtained in 20 healthy volunteers, patient's NK activity was decreased (4.6 ñ 3.9 vs 26.1 ñ 10, p < 0.025), CD16 was lower (10%/187 vs 15%/280 per ul) and CD56 was also lower (6%/120 vs 12%/224 per ul), p < 0,05. T lymphocyte subsers were also decreased: CD3 cells (1100 vs 1352 per ul) and CD4 cells (634 vs 873 per ul), p < 0.05. Thus, a severe decrease in NK cells and NK cell function as well as decreases in CD3 and CD4 lymphocyte subsets are present in the initial stages of septic shock. The predictive value of these findings is currently under study