RESUMEN
On August 22-23, 2013, agencies within the United States Department of Defense (DoD) and the Department of Health and Human Services (HHS) sponsored the Filovirus Medical Countermeasures (MCMs) Workshop as an extension of the activities of the Filovirus Animal Non-clinical Group (FANG). The FANG is a federally-recognized multi-Agency group established in 2011 to coordinate and facilitate U.S. government (USG) efforts to develop filovirus MCMs. The workshop brought together government, academic and industry experts to consider the needs for filovirus MCMs and evaluate the status of the product development pipeline. This report summarizes speaker presentations and highlights progress and challenges remaining in the field.
Asunto(s)
Anticuerpos Antivirales/biosíntesis , Infecciones por Filoviridae/prevención & control , Filoviridae/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Neutralizantes/administración & dosificación , Filoviridae/patogenicidad , Infecciones por Filoviridae/inmunología , Infecciones por Filoviridae/virología , Cobayas , Haplorrinos , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Ratones , Estados Unidos , United States Department of Defense , United States Dept. of Health and Human Services , Vacunas de ADN , Vacunas Virales/administración & dosificación , Vacunas Virales/biosíntesis , Replicación Viral/efectos de los fármacosRESUMEN
GATA-3 and T-box expressed in T cells (T-bet) play central roles in Th-cell development and function. Consistently, studies in mice document their selective expression in Th1 and Th2 cells, respectively. In contrast, it is not clear whether these genes are regulated in human Th cells. Here we show that T-bet expression is polarized to a comparable degree in human and mouse Th-cell cultures, while only mouse GATA3 is subject to substantial regulation. This did not reflect differential skewing efficiency in human versus mouse cultures, as these contained similar frequencies of IFN-gamma- and IL-4-producing cells. However, GATA-3 was expressed at significantly higher levels in human IL-4-producing cells enriched via capture with monoclonal antibodies (mAbs) against the PGD(2) receptor, CRTH2, the best selective Th2-cell surface marker to date. Along with increased IL-4 and GATA-3, CRTH2(+) Th cells isolated from Th2-skewed cultures or the circulating memory pool exhibited markedly decreased IFN-gamma and T-bet expression. Thus, the human GATA-3 gene is not regulated in response to polarizing signals that are sufficient to direct Th2-specific expression in mouse cells. This postulates the involvement of an additional level of complexity in the regulation of human GATA-3 expression and stresses the existence of nontrivial differences in the regulation of human versus mouse T-cell function.