Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude.

TNF is a pro-inflammatory cytokine produced by both lymphoid and non-lymphoid cells. As a consequence of the widespread expression of its receptors (TNFR1 and 2), TNF plays a role in many important biological processes. In the context of influenza A virus (IAV) infection, TNF has variably been implicated in mediating immunopathology as well as suppression of the immune response. Although a number of cell types are able to produce TNF, the ability of CD8+ T cells to produce TNF following viral infection is a hallmark of their effector function. As such, the regulation and role of CD8+ T cell-derived TNF following viral infection is of great interest. Here, we show that the biphasic production of TNF by CD8+ T cells following in vitro stimulation corresponds to distinct patterns of epigenetic modifications. Further, we show that a global loss of TNF during IAV infection results in an augmentation of the peripheral virus-specific CD8+ T cell response. Subsequent adoptive transfer experiments demonstrated that this attenuation of the CD8+ T cell response was largely, but not exclusively, conferred by extrinsic TNF, with intrinsically-derived TNF making only modest contributions. In conclusion, TNF exerts an immunoregulatory role on CD8+ T cell responses following IAV infection, an effect that is largely mediated by extrinsically-derived TNF

Conjoined lumbosacral nerve roots: observations on three cases and review of the literature

Lumbosacral nerve root anomalies are a rare group of congenital anatomical anomalies. Various types of anomalies of the lumbosacral nerve roots have been documented in the available international literature. Generally speaking, these anomalies may consist of a bifid, conjoined structure, of a transverse course or of a characteristic anastomized appearance. Firstly described as an incidental finding during autopsies or surgical procedures performed for lumbar disk herniations and often asymptomatic, lumbosacral nerve root anomalies have been more frequently described in the last years due to the advances made in radiological diagnosis (metrizamide myelography and CT, MRI). Our study comprised three patients with conjoined lumbosacral nerve roots, representing 0.25% of a total of 1200 patients who underwent lumbosacral CT/MRI procedures in the Addolorata Hospital and in the Service of Neuroradiology of the University of Rome "La Sapienza" during the last three years (March 2001-March 2004). We report our experience with three cases of conjoined lumbosacral nerve roots and analyze the most important literature on this topic. MR imaging is a better diagnostic procedure (in comparison to CT) for the differentiation of nerve root anomalies and, in particular, coronal sections furnish a precise definition of the profile of the conjoined/enlarged rootlets. In fact, the accurate information derived from MRI of multiple planes may be priceless for the preoperative and diagnostic evaluation of lumbosacral nerve root anomalies