RESUMEN
Recent data have indicated that CD8+ T cells suppress rodent IgE responses. In this study we investigated the effect of CD8+ T cells on primary and established IgE responses in euthymic and athymic nude rats. Euthymic PVG rats were depleted of CD8+ T cells by intraperitoneal injection of a CD8-specific monoclonal antibody (OX8), which resulted in an apparent loss of 92% of splenic and 98% of peripheral blood CD8+ T cells. The CD8+ T-cell depleted animals failed to mount a significant IgE response compared with control animals given an irrelevant monoclonal antibody (OX21). Furthermore, PVG nude rats reconstituted with purified CD4+ thoracic duct lymphocytes (TDL) alone failed to mount a significant IgE response, while animals given unfractionated TDL (containing CD4+ and CD8+ T cells) did. Depletion of CD8+ T cells 7 days prior to immunization and subsequent reconstitution at the time of immunization restored the IgE response. In contrast, removal of CD8+ T cells 1 month after induction of IgE by immunization with ovalbumin (OVA) and ricin prolonged the IgE response. In all cases IgG antibody responses were unaffected by the presence or absence of CD8+ T cells. This study shows that some CD8+ T cells are required for IgE, but not IgG, production to soluble antigen in a primary immune response. However, later in the immune response CD8+ T cells were shown to inhibit IgE production. These effects were apparently restricted to the immune response to soluble antigen, as Hooded Lister rats infected with 9000 larvae of the nematode Nippostrongylus brasiliensis produced high sustained levels of circulating IgE, in excess of 10 micrograms/ml, regardless of whether CD8+ T cells were depleted before or 1 month after infection.
Asunto(s)
Antígenos Helmínticos/inmunología , Linfocitos T CD8-positivos/inmunología , Inmunoglobulina E/fisiología , Nippostrongylus/inmunología , Animales , Inmunización , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Ratas , Ratas Endogámicas , Ratas Desnudas , Bazo/inmunología , TimectomíaAsunto(s)
Etnicidad/psicología , Control Interno-Externo , Neoplasias/psicología , Adulto , Negro o Afroamericano/psicología , Anciano , Actitud Frente a la Salud , Cultura , Escolaridad , Femenino , Hispánicos o Latinos/psicología , Humanos , México/etnología , Persona de Mediana Edad , Neoplasias/etnología , Neoplasias/prevención & control , Estados Unidos , Población Blanca/psicologíaRESUMEN
A 25-year old patient with chronic granulomatous disease of somewhat unusual history is described. The diagnosis of CGD was based on increased susceptibility to infection, granulomatous appearance of tissues, and diminished bactericidal and metabolic response of leukocytes during phagocytosis: the clinical and cellular features considered phenotypic of CGD. A 16-year-old female sibling had bactericidal and metabolic abnormalities of leukocyte function similar to those of the patient's leukocytes. Leukocytes from another sister, 26 years of age, were intermediate in bactericidal capacity. Two populations of leukocytes were identified by a histochemical test of NBT reduction. Both normal and abnormal polymorphonuclear leukocytes were present in the leukocyte population of the two sisters. Leukocytes from the patient's mother and maternal grandmother were normal by all methods tested. These findings are taken as evidence of a germ-line mutation in the chromosomal gene causing CGD, with transmission of the genetic defect from the mother to the son.
Asunto(s)
Cromosomas , Enfermedad Granulomatosa Crónica/genética , Disfunción de Fagocito Bactericida/genética , Adulto , Actividad Bactericida de la Sangre , Enterococcus faecalis , Femenino , Enfermedad Granulomatosa Crónica/metabolismo , Hexosafosfatos/metabolismo , Humanos , Yoduros/metabolismo , Leucocitos/metabolismo , Masculino , Nitroazul de Tetrazolio/metabolismo , Consumo de Oxígeno , Fagocitosis , Proteus mirabilis , Staphylococcus aureus , Zimosan/metabolismoRESUMEN
Bactericidal and metabolic activities were compared for polymorphonuclear leukocytes from normal controls, patients with sex-linked chronic granulomatous disease, five obligate carriers, and six potential carriers of CGD. Bacteria surviving at one hour were quantitated in a standardized assay which employed 1.25 Staphylococcus aureus per neutrophil. Heat-killed bacteria or a chemical agent, phorbol myristate acetate, were used to stimulate increases in utilization of oxygen, oxidation of [1--14C] glucose, and reduction of neotetrazolium chloride by PMN. The results demonstrate that PMN from the individual obligate carriers of CGD have a broad spectrum of functional capabilities. Neutrophils from one obligate carrier performed in the above in vitro tests and others on a par with normal control cells, whereas the PMN of others displayed deficiencies nearly as profound as those of the affected CGD patients. The observations parallel the broad range of phenotypic expression observed in heterozygotic carriers of other sex-linked recessive disorders as a result of random inactivation of the X chromosome. Although predictable from the current concept of random X inactivation, the spectrum has not been previously demonstrated for carriers of sex-linked recessive CGD and thus has important implications for the detection and counseling of carriers of CGD.