RESUMEN
CD8(+) T-cell responses against latent viruses can cover considerable portions of the CD8(+) T-cell compartment for many decades, yet their initiation and maintenance remains poorly characterized in humans. A key question is whether the clonal repertoire that is raised during the initial antiviral response can be maintained over these long periods. To investigate this we combined next-generation sequencing of the T-cell receptor repertoire with tetramer-sorting to identify, quantify and longitudinally follow virus-specific clones within the CD8(+) T-cell compartment. Using this approach we studied primary infections of human cytomegalovirus (hCMV) and Epstein Barr virus (EBV) in renal transplant recipients. For both viruses we found that nearly all virus-specific CD8(+) T-cell clones that appeared during the early phase of infection were maintained at high frequencies during the 5-year follow-up and hardly any new anti-viral clones appeared. Both in transplant recipients and in healthy carriers the clones specific for these latent viruses were highly dominant within the CD8(+) T-cell receptor Vß repertoire. These findings suggest that the initial antiviral response in humans is maintained in a stable fashion without signs of contraction or changes of the clonal repertoire.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Receptores de Antígenos de Linfocitos T/genética , Antígenos Virales/inmunología , Citomegalovirus/genética , Herpesvirus Humano 4/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Trasplante de Riñón/inmunología , Persona de Mediana Edad , Factores de Tiempo , Latencia del Virus , Adulto JovenRESUMEN
Several assays to measure pre-existing allospecific T cell immunity in renal transplant candidates have been developed in the past years. In 46 patients, we used flow cytometry-based mixed lymphocyte culture to measure the precursor frequency and phenotype of alloreactive T cells before renal transplantation, using donor-specific or third-party cells for allostimulation. Allostimulation induced up-regulation of co-stimulatory molecules, chemokine receptors relevant for migration of T cells into the graft and effector proteins. Recipients prone for acute rejection had a higher precursor frequency of alloreactive CD8(+) T cells and a lower percentage of interleukin (IL)-7Rα expressing alloreactive CD8(+) T cells than non-rejectors. These data point to quantitative and qualitative differences between T cells of patients who will experience acute cellular rejection episodes from those who will not.
Asunto(s)
Trasplante de Riñón/inmunología , Linfocitos T/inmunología , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Femenino , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/inmunología , Humanos , Inmunofenotipificación , Interferón gamma/metabolismo , Subunidad alfa del Receptor de Interleucina-15/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Activación de Linfocitos/inmunología , Recuento de Linfocitos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Persona de Mediana Edad , Receptores de Quimiocina/metabolismo , Receptores de Citocinas/metabolismo , Receptores de Interleucina-7/metabolismo , Donantes de Tejidos , Trasplante Homólogo/inmunologíaRESUMEN
As middle managers, medical record practitioners will be involved in justification of auto ID technology to upper management. To prepare a good justification, one must have a thorough knowledge of the technology and its advantages and disadvantages. One must also be familiar with the payback period and the installation process. This article has attempted to introduce the reader to some emerging technologies in health care, and answer some of the questions that are key to justifying their acquisition. By most estimates, these technologies are finding their way into health care, however slowly, and hold much promise for improvement in productivity and accuracy in data collection.