Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens.

Activation of self-reactive CD8+ T cells induces a peripheral tolerance mechanism that involves loss of CD8 expression. Because genetic deficiency of Fas and Fasl causes the accumulation of double-negative (DN; CD3+ TCR-αß+ CD4- CD8-) T cells that have been proposed to derive from CD8+ cells, we decided to explore the role of Fas and FasL in self-antigen-induced CD8 downregulation. To this end, we quantified Fas and FasL induction by different stimuli and analyzed the effects of Fas/FasL deficiency during a protective immune response and after exposure to self-antigens. Our data describes how Fas and FasL upregulation differs depending on the setting of CD8 T cell activation and demonstrates that Fas/FasL signaling maintains CD8 expression during repetitive antigen stimulation and following self-antigen encounter. Together, our results reveal an unexpected role of Fas/FasL signaling and offer a new insight into the role of these molecules in the regulation of immune tolerance.

TCR-α/ß CD4- CD8- double negative T cells arise from CD8+ T cells.

The cellular origin of CD4- CD8- (double negative, DNT) TCR-α/ß+ T cells remains unknown. Available evidence indicates that they may derive from CD8+ T cells, but most published data have been obtained using cells that bear an invariant transgenic T cell receptor that recognizes an Ag that is not present in normal mice. Here, we have used complementary fate mapping and adoptive transfer experiments to identify the cellular lineage of origin of DNT cells in wild-type mice with a polyclonal T cell repertoire. We show that TCR-α/ß+ DNT cells can be traced back to CD8+ and CD4+ CD8+ double positive cells in the thymus. We also demonstrate that polyclonal DNT cells generated in secondary lymphoid organs proliferate upon adoptive transfer and can regain CD8 expression in lymphopenic environment. These results demonstrate the cellular origin of DNT cells and provide a conceptual framework to understand their presence in pathological circumstances.

Mechanisms of Tissue Injury in Lupus Nephritis.

Disease heterogeneity remains a major challenge for the understanding of systemic lupus erythematosus (SLE). Recent work has revealed the important role of nonimmune factors in the development of end-organ damage involvement, shifting the current paradigm that views SLE as a disease inflicted by a disturbed immune system on passive target organs. Here, we discuss the pathogenesis of lupus nephritis in a comprehensive manner, by incorporating the role that target organs play by withstanding and modulating the local inflammatory response. Moreover, we consider the effects that genetic variants exert on immune and nonimmune cells in order to shape the phenotype of the disease in each affected individual.

Prueba de Elisa indirecta del lisado total de bartonella bacilliformis para el diagnóstico rápido de la enfermedad de Carrión / Indirect Elisa of Bartonella bacilliformis total lysate for quick diagnosis of Carrion disease

Se elaboró y estandarizó una prueba de ELISA indirecta con el lisado total de Bartonella bacilliformis procedentes de una cepa ATCC y de un aislamiento clínico. Se seleccionaron 86 sueros de pacientes con diagnóstico confirmado de enfermedad de Carrión por frotis ycultivo, 51 sueros negativos de pacientes de zonas no endémicas y 32 sueros de pacientes con diagnóstico serológico confirmado para otras enfermedades bacterianas como brucelosis, leptospirosis, sífilis y Rickettsiosis. Se encontró una sensibilidad de 68,6 por ciento (IC95 por ciento: 58,2-79,0 por ciento), especificidad de 94,1 por ciento (86,7-100 por ciento), valor predictivo positivo de 95,2 por ciento (89,0-100 por ciento) y valor predictivo negativo de 64,0 por ciento (54,3-71,2 por ciento), con una reacción cruzada con otras etiologías bacterianas de 78,1 por ciento (25/32). Esta no es una prueba idónea para ser usada como herramienta diagnóstica para la Enfermedad de Carrión, se debe continuar los estudios hacia la búsqueda de una prueba rápida con mayor sensibilidad.

Was developed and standardized an indirect ELISA test with the total lysate of Bartonella bacilliformis from an ATCC strain and a clinical isolation. We selected 86 sera from patients with confirmed diagnosis of Carrion disease by smear and culture, 51 sera of negative patients for non-endemic areas and 32 sera from patients with confirmed serological diagnosis for other bacterial diseases such as brucellosis, leptospirosis, syphilis and Rickettsiosis. We found a sensitivity of 68.6 per cent (95 per cent CI: 58.2-79.0 per cent), specificity of 94.1 per cent (86.7-100 per cent), positive predictive value of 95.2 per cent (89.0 -100 per cent) and negative predictive value of 64.0 per cent (54.3-71.2 per cent), with a cross-reaction with other bacterial aetiologies of 78.1 per cent (25/32). This is not a recommended test to be used as a diagnostic tool for Carrion disease, is continuing studies toward finding a quick test with greater sensitivity.