RESUMO
In this study we searched for circulating antibodies or other serum factors that could account for the natural killer (NK) defect observed in hemophiliacs (He) infected with the human immunodeficiency virus (HIV). We analyzed the effect of negative or positive sera for HIV from He on normal NK activity. We showed that sera from He interfered with normal NK cytotoxicity. The inhibitory activity was higher in HIV+ sera and increased as the HIV disease progressed. HIV- sera also inhibited NK function, although to a lesser extent than HIV+, and it was probably due to isoimmunization through replacement treatment with plasma-derived concentrates. For each individual, no direct correlation was found between NK inhibition (NK-INH) of sera and the NK activity of He peripheral blood mononuclear cells (PBMC). Furthermore, He serum was poorly inhibitory on autologous PBMC. Preincubation of allogenic effector or target cells with He sera revealed that the inhibitory effect was the result of the reaction with these cells. A positive correlation was found by comparing NK-INH of whole He sera with the serum levels of circulating immune complexes. When the NK-INH assay was performed using the same concentration of DEAE-purified IgG from N, HIV- or HIV+, we found that HIV+ AIDS IgG was more inhibitory than the others.
Assuntos
Infecções por HIV/sangue , Hemofilia A/sangue , Imunoglobulina G/imunologia , Síndromes de Imunodeficiência/etiologia , Células Matadoras Naturais/imunologia , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/complicações , Complexo Antígeno-Anticorpo/sangue , Complexo Antígeno-Anticorpo/imunologia , Testes Imunológicos de Citotoxicidade , Citotoxicidade Imunológica , Infecções por HIV/complicações , Soropositividade para HIV , Hemofilia A/complicações , Hemofilia B/sangue , Hemofilia B/complicações , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/isolamento & purificação , Células Matadoras Naturais/patologia , Leucócitos Mononucleares/imunologiaRESUMO
In this study we analyzed the ability of peripheral blood mononuclear cells (PBMC) from hemophilic patients (He) with negative or positive serology for the human immunodeficiency virus (HIV), to increase natural killer (NK) cytotoxicity upon stimulation with physiological and non physiological agents. Purified interleukin-2 (IL-2), the interferon (IFN)-inducer polyinosinic polycytidylic acid (PIC), recombinant alpha- and gamma-IFN and the protein kinase activator phorbol myristate acetate (PMA) were used as stimulatory agents. The NK functional response was correlated with the presence of PBMC bearing phenotypic markers of activated cells (IL-2 receptor, IL-2R) and of different NK cell maturation stages. Our results demonstrate that NK effector cells with slight lytic activity (Leu 7+ CD16-) predominated in HIV+ He patients. On the other hand the occurrence of IL-2R positive cells was similarly high in both HIV+ and HIV- individuals and was probably more related to chronic replacement treatment with Factor VIII or Factor IX concentrates than to HIV infection. The ability to respond to physiological NK regulators such as IL-2 and IFNs, or to the IFN-inducer PIC was impaired in HIV+ He, especially in HIV+ LAS individuals, suggesting that the inability of these cells to increase NK cell activity after appropriate induction was due to an intrinsic defect. Since phosphoinositide turnover and subsequent protein kinase C activation are thought to be part of the physiological mechanism of NK cytotoxicity, we studied the effect of PMA on PBMC from each group of patients. The ability to respond to PMA was lost only in PBMC from HIV+ LAS patients, indicating that impairment of the NK lytic mechanism progresses as the disease gets worse.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Infecções por HIV/imunologia , Hemofilia A/imunologia , Células Matadoras Naturais/imunologia , Antígenos de Diferenciação/análise , Citotoxicidade Imunológica/efeitos dos fármacos , Infecções por HIV/complicações , Hemofilia A/complicações , Humanos , Interleucina-2/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Fenótipo , Receptores de Interleucina-2/análise , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Se estudio la actividad citotoxica de los leucocitos mononucleares (LM) y polimorfonucleares (PMN) de pacientes chagasicos cronicos contra epimastigotes de Trypanosoma cruzi en presencia de anticuerpos (suero autologo o de conejo inmune). Ambas clases de leucocitos fueron capaces de lisar los epimastigotes pero no se observo actividad citotoxica directa de los LM o PMN contra T. cruzi. La actividad promotora de la citotoxicidad y la fagocitosis de PMN del suero de los pacientes chagasicos se encontro en las fracciones de constante de sedimentacion 7S, asociada a la actividad aglutinante resistente a 2-ME indicando que se trata de IgG inmune. Este mecanismo podria ser activo en los pacientes chagasicos como barrera en la diseminacion de los parasitos
Assuntos
Humanos , Doença de Chagas , Citotoxicidade Imunológica , Leucócitos , Trypanosoma cruziRESUMO
Se estudio la actividad citotoxica de los leucocitos mononucleares (LM) y polimorfonucleares (PMN) de pacientes chagasicos cronicos contra epimastigotes de Trypanosoma cruzi en presencia de anticuerpos (suero autologo o de conejo inmune). Ambas clases de leucocitos fueron capaces de lisar los epimastigotes pero no se observo actividad citotoxica directa de los LM o PMN contra T. cruzi. La actividad promotora de la citotoxicidad y la fagocitosis de PMN del suero de los pacientes chagasicos se encontro en las fracciones de constante de sedimentacion 7S, asociada a la actividad aglutinante resistente a 2-ME indicando que se trata de IgG inmune. Este mecanismo podria ser activo en los pacientes chagasicos como barrera en la diseminacion de los parasitos