RESUMEN
The purpose of this study was to look for associations between a newly described class of suppressors of cytokine signaling (SSI/SOCS) and cytokine expression in the uterine cervix from HIV/HPV coinfected women. We examined the pro-inflammatory cytokines TNF-alpha and IL-6 since their expressions are linked and responsible for many aspects of both localized and systemic inflammatory responses. Further, expression of SSI/SOCS has been implicated in the negative feedback regulation of cytokine receptor signaling. PCR-amplified HIV-1 cDNA was noted mainly in the stroma, showing a perivascular distribution, and most of the infected cells colabeled with the macrophage marker CD68. The distribution of IL-6 and TNF-alpha was in the same area to HIV-1 and much greater than normal cervices from women with no evidence of viral infection. SOCS/SSI-1 and -3 mRNA positive cells in the uterine cervix were commonly detected in these noninfected cervical tissues; however, very few cells that contained SOCS were evident in areas where HIV-1, TNF-alpha, and IL-6 expressing cells were found. This suggests that viral-related suppression of SOCS/SSI-1-3 expression may be a factor in the marked local enhancement of TNF-alpha and IL-6 production which, in turn, may help facilitate viral spread; however, further studies should be done in order to elucidate the exact mechanisms of SOCS in the cervix.
Asunto(s)
Cuello del Útero/metabolismo , Infecciones por VIH/metabolismo , Interleucina-6/metabolismo , Papillomaviridae , Infecciones por Papillomavirus/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Antígeno B7-2/genética , Antígeno B7-2/metabolismo , Cuello del Útero/inmunología , Cuello del Útero/patología , Citocinas/genética , Citocinas/metabolismo , ADN Viral/análisis , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , VIH-1/aislamiento & purificación , Humanos , Interleucina-6/genética , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/inmunología , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Proteínas Supresoras de la Señalización de Citocinas/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Much has been learned about how HIV-induced immune dysfunction contributes to B cell hyperactivation, and potentially, to the pathogenesis of AIDS-lymphoma. However, further studies are needed to fully understand how HIV infection and immune dysfunction promote B cell hyperactivation and the development/growth of AIDS-lymphoma. In particular, studies are needed to define the role of HHV8 vIL6, IL6 receptor-expression, and lymphocyte surface stimulatory molecules, in promoting B cell hyperactivation or lymphoma cell growth.
Asunto(s)
Linfocitos B/patología , Linfoma Relacionado con SIDA/inmunología , Linfoma no Hodgkin/inmunología , División Celular/inmunología , Citocinas/inmunología , Herpesvirus Humano 8/inmunología , Herpesvirus Humano 8/patogenicidad , Humanos , Linfoma Relacionado con SIDA/patología , Linfoma no Hodgkin/patología , Receptores de Interleucina-6/inmunologíaRESUMEN
The temporal relationship of serum levels of human immunodeficiency virus (HIV) RNA and of immune activation products in 10 HIV-seropositive persons who showed an accelerated decline (inflection point) in CD4 T cell counts and went on to develop AIDS and in 10 matched controls without inflection point were examined. Cases and controls did not differ statistically at the baseline time point for this study. CD4 cell inflection points occurred 18-30 months before AIDS development. Serum levels of soluble tumor necrosis factor receptor II, soluble interleukin-2 receptor, beta2-microglobulin, and neopterin increased significantly > or = 6 months before the CD4 cell inflection point. In contrast, increases in mean HIV RNA levels occurred at the time of the CD4 cell inflection point. These data are consistent with the view that in vivo immune activation precedes the increases in virus load and is followed by an accelerated and rapid loss of CD4 lymphocytes.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Seropositividad para VIH/inmunología , VIH-1/inmunología , Activación de Linfocitos/inmunología , Carga Viral , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/fisiopatología , Síndrome de Inmunodeficiencia Adquirida/virología , Complejo CD3/inmunología , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos/inmunología , Estudios de Casos y Controles , Progresión de la Enfermedad , Seropositividad para VIH/fisiopatología , Seropositividad para VIH/virología , Homosexualidad Masculina , Humanos , Masculino , ARN Viral/sangreRESUMEN
There are evidences regarding the role of NK cytotoxic activity in the resistance against experimental C. neoformans infection. To assess the status of NK cell activity in human C. neoformans infection, we studied the peripheral blood of twelve patients with cryptococcal meningitis, six patients with CNS disease different to cryptococcal meningitis, and twelve healthy subjects. The number of CD16+cells and the NK cytotoxic activity of peripheral blood mononuclear cells was studied. The in vitro effect of exogenous IL-2 and interferon gamma on such cytotoxic activity was also studied. The number of CD16+ cells was not significantly different in patients compared to controls. However, cryptococcal patients exhibited a significant lower NK activity compared to both control groups (p less than 0.05 in both cases). The low NK activity of cryptococcal patients was fully reconstituted in vitro with the addition of rIL-2 but not with rIFN gamma. In vitro experiments suggest that the low NK activity of cryptococcal meningitis patients is not due to amphotericin B therapy or blockade of NK cells by C. neoformans-derived molecules. The results of this study suggests that patients with cryptococcal meningitis have a defective NK cytotoxic function and may aid to understand the pathogenesis of this disease.