RESUMEN
We have recently reported that IL 2-activated killer (LAK) cells are capable of lysing cultured human monocytes. In an effort to protect autologous monocytes from lysis, we treated monolayer cultures of adherent PBMC with various doses of human rIFN-gamma and assessed their susceptibility to LAK cells. IFN-gamma was shown to lessen the sensitivity of monocytes to lysis in a dose-dependent manner. Similar treatment of FMEX, an NK-resistant melanoma tumor cell line, with IFN-gamma did not affect its susceptibility to LAK lysis. Kinetic studies demonstrated that as little as 2 h incubation with IFN-gamma was sufficient for the protective effects to take effect. Additionally, monocytes that were pulsed with IFN-gamma for 2 h, washed, and then cultured in medium alone retained their resistance to lysis for at least 3 days. Cold target inhibition studies showed that IFN-treated and untreated monocytes could effectively compete with each other for binding sites on LAK cells. Furthermore, binding studies demonstrated that there was no significant difference between the number of conjugates formed by using either IFN-treated or untreated monocytes. This indicates that resistance to lysis induced by IFN treatment affects a post-binding event and not an initial recognition signal. From these studies, it was apparent that treatment of monocytes with IFN-gamma lessened their sensitivity to LAK-mediated lysis. Thus, it may be possible through a specific sequence of IFN-gamma and IL-2 treatment that LAK activity could be manipulated against some tumor cells, but not normal cells, to abrogate some of the toxicity seen with this type of cancer therapy.
Asunto(s)
Citotoxicidad Inmunológica/efectos de los fármacos , Interferón gamma/farmacología , Interleucina-2 , Células Asesinas Naturales/inmunología , Monocitos/inmunología , Células Cultivadas , Humanos , Inmunidad Innata/efectos de los fármacos , Interferón Tipo I/farmacología , Monocitos/clasificación , Monocitos/metabolismo , Fenotipo/efectos de los fármacos , Biosíntesis de Proteínas , ARN/biosíntesis , Proteínas Recombinantes/farmacología , Factores de TiempoRESUMEN
A previously established human leukemia cell line, designated THP-6, was further characterized with respect to cell surface antigen expression and immunoglobulin(Ig) and T-cell receptor(TCR) gene status. THP-6 cells were positive for CD7 and CD5 antigens and terminal deoxynucleotidyl transferase, but negative for CD2, CD1, CD4, CD8, CD10, cytoplasmic and surface CD3 and HLA-DR antigens, suggesting a precursor T-cell line. Analysis of Ig and TCR beta chain genes revealed that THP-6 had a rearranged TCR beta chain gene and a germline Ig gene. These results, in agreement with its phenotype, confirmed that THP-6 was of the T-cell lineage.
Asunto(s)
Genes de Inmunoglobulinas , Células Madre Hematopoyéticas/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T/metabolismo , Línea Celular , Niño , Medios de Cultivo/farmacología , Dimetilsulfóxido/farmacología , Femenino , Células Madre Hematopoyéticas/clasificación , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Fenotipo/efectos de los fármacos , Fitohemaglutininas/farmacología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Linfocitos T/clasificación , Linfocitos T/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacologíaAsunto(s)
Bromodesoxiuridina/farmacología , Fenotipo/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Animales , Formación de Anticuerpos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Depresión Química , Inducción Enzimática/efectos de los fármacos , Ácido Hialurónico/biosíntesis , Ratones , Neuroblastoma/patología , Conejos , Ratas , Bazo/efectos de los fármacos , Tirosina Transaminasa/metabolismoRESUMEN
d-Cycloserine (d-CS), a selective inhibitor of bacterial cell wall biosynthesis, inhibited transformation in group H streptococcus, strain Challis, by preventing the development of the competent state. The incubation of strain Challis cells with d-CS resulted in the production of a substance which inhibited the action of competence factor on these cells. d-CS had an enhancing effect on transformation when deoxyribonucleic acid uptake or phenotypic expression was allowed to occur in its presence.