RESUMEN
The CD7(-) subset of CD4(+) T cells reflects a stable differentiation state of post-thymic helper T cells with CD45R0(+)CD45RA(-) 'memory' phenotype. Here we report that CD4(+)CD7(-) T cells are prone to increased spontaneous apoptosis in vitro compared to CD4(+)CD7(+) T cells. Spontaneous apoptosis is prevented by IL-15, but not by IL-2. Moreover, IL-15 increases Bcl-2 and decreases CD95/Fas expression of CD7(-), but not of CD7(+) T cells. Because IL-15 is physiologically not secreted but expressed in a membrane-bound form, we cocultured T cells with TNF-alpha stimulated fibroblasts that expose membrane IL-15. TNF-alpha stimulated fibroblasts rescue CD4(+)CD7(-) T cells from apoptosis whereas unstimulated fibroblasts do not. Rescue from apoptosis requires cell-cell contact and is abolished by addition of neutralizing antibodies to IL-15. We conclude that membrane IL-15 prevents accelerated apoptosis of CD4(+)CD7(-) T cells. This mechanism may contribute to accumulation of CD7(-) T cells in chronic inflammatory skin lesions.
Asunto(s)
Antígenos CD7/análisis , Apoptosis , Linfocitos T CD4-Positivos/inmunología , Dermatitis/inmunología , Interleucina-15/farmacología , Subgrupos de Linfocitos T/inmunología , Apoptosis/efectos de los fármacos , Linfocitos T CD4-Positivos/citología , Células Cultivadas , Dermis/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Humanos , Memoria Inmunológica , Inmunofenotipificación , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptores de Interleucina-15 , Receptores de Interleucina-2/metabolismo , Subgrupos de Linfocitos T/clasificación , Subgrupos de Linfocitos T/citología , Factor de Necrosis Tumoral alfa/farmacología , Receptor fas/metabolismoRESUMEN
It has been suggested that extracellular mRNA might be released from tumor cells and might be protected from serum RNase by proteins or proteolipid complexes. Our group has recently assessed the potential value of extracellular RNA detection by RT-PCR in the peripheral blood of patients with metastatic melanoma.
Asunto(s)
Melanoma/sangre , ARN Mensajero/sangre , ARN Neoplásico/sangre , Antígenos de Neoplasias , Humanos , Antígeno MART-1 , Melanoma/genética , Melanoma/patología , Monofenol Monooxigenasa/genética , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Células Neoplásicas Circulantes , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Recently, Chlamydia pneumoniae-specific DNA and antigens were reported in the skin of patients with Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphomas. In order to revalidate these data we analyzed skin sections of patients with MF for the expression of three different chlamydial antigens and C. pneumoniae DNA by immunohistochemistry and PCR according to previously described protocolls. Neither C. pneumoniae-specific DNA sequences nor antigens were detected in any of the skin biopses from 24 MF patients tested, suggesting that further studies are needed to establish any pathogenetic relevance of C. pneumoniae in MF.
Asunto(s)
Infecciones por Chlamydophila/fisiopatología , Chlamydophila pneumoniae , Micosis Fungoide/fisiopatología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Micosis Fungoide/microbiologíaRESUMEN
Reverse transcription polymerase chain reaction (RT-PCR)-based detection of tyrosinase mRNA is a frequently used method for the identification of circulating tumor cells in melanoma patients. The significance and practical value of this procedure for the diagnosis of tumor dissemination in melanoma patients are unclear. The conflicting results may at least partially be related to very low amounts of circulating tumor cells and to our observation that melanoma cells only transiently persist in the peripheral blood. The purpose of the present study was to evaluate the relevance of detection of extracellular melanoma-specific mRNA in serum and plasma samples in comparison to blood cell samples from patients with disseminated disease (stage IV). We therefore compared the presence of specific mRNA for tyrosinase, gp100, and MART-1 by RT-PCR amplification of specific cDNA from serum, plasma, and whole blood samples of 10 melanoma patients. Melanoma-specific mRNA was detectable in whole blood samples of all ten patients tested indicating the presence of circulating melanoma cells. In addition, tyrosinase mRNA could be detected in the serum and/or plasma of 6 of 10 melanoma patients whereas gp100 and MART-1 specific transcripts were not detectable in any of the samples tested. The presence and integrity of amplifiable RNA was shown in all serum and plasma samples of patients and controls by RT-PCR-specific amplification of porphobilinogen deaminase (PBDG) mRNA. We conclude that tyrosinase mRNA but not gp100 and MART-1 mRNA can be amplified from serum and/or plasma in a subset of melanoma patients showing circulating melanoma cells. Therefore, extracellular-directed assays appear to be less sensitive and efficacious in detecting melanoma-specific transcripts compared to cellular-based assays.
Asunto(s)
Biomarcadores de Tumor/sangre , Melanoma/sangre , Proteínas de Neoplasias/genética , Células Neoplásicas Circulantes , ARN Mensajero/sangre , ARN Neoplásico/sangre , Adulto , Anciano , Antígenos de Neoplasias , Biomarcadores de Tumor/genética , Células Sanguíneas/química , Femenino , Humanos , Hidroximetilbilano Sintasa/genética , Antígeno MART-1 , Masculino , Melanoma/genética , Melanoma/patología , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Monofenol Monooxigenasa/genética , Metástasis de la Neoplasia , Plasma , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Antígeno gp100 del MelanomaRESUMEN
Glomus tumors are benign tumors and are most often localized acral. They usually are diagnosed non-invasively by patient's history, clinical examination, duplex ultrasound and MRI-angiography. Need for intervention depends on the symptoms.