Levels Of IL-12 In Supernatants Research Articles

The Immunosuppressive Properties of the HIV Vpr Protein Are Linked to a Single Highly Conserved Residue, R90

BackgroundA hallmark of AIDS progression is a switch of cytokines from Th1 to Th2 in the plasma of patients. IL-12, a critical Th1 cytokine secreted by antigen presenting cells (APCs) is suppressed by Vpr, implicating it as an important virulence factor. We hypothesize that Vpr protein packaged in the virion may be required for disabling APCs of the first infected mucosal tissues. Consistent with this idea are reports that defects in the C-terminus of Vpr are associated with long-term non-progression.Principal FindingsVpr RNA amplified from various sources was electroporated into monocyte-derived DC and IL-12 levels in supernatants were analyzed. The analysis of previously reported C-terminal Vpr mutations demonstrate that they do not alleviate the block of IL-12 secretion. However, a novel single conservative amino acid substitution, R90K, reverses the IL-12 suppression. Analysis of 1226 Vpr protein sequences demonstrated arginine (R) present at position 90 in 98.8%, with other substitutions at low frequency. Furthermore, none of sequences report lysine (K) in position 90. Vpr clones harboring the reported substitutions in position 90 were studied for their ability to suppress IL-12. Our data demonstrates that none of tested substitutions other than K relieve IL-12 suppression. This suggests a natural selection for sequences which suppress IL-12 secretion by DC and against mutations which relieve such suppression. Further analyses demonstrated that the R90K, as well as deletion of the C-terminus, directs the Vpr protein for rapid degradation.ConclusionThis study supports Vpr as an HIV virulence factor during HIV infection and for the first time provides a link between evolutionary conservation of Vpr and its ability to suppress IL-12 secretion by DC. DC activated in the presence of Vpr would be defective in the production of IL-12, thus contributing to the prevailing Th2 cytokine profile associated with progressive HIV disease. These findings should be considered in the design of future immunotherapies that incorporate Vpr as an antigen.

A depressed peripheral cellular immune response is related to symptomatic neurocysticercosis

Human neurocysticercosis can cause mild or severe neurological symptoms or be completely asymptomatic. This heterogeneity may depend on host factors such as gender, age and immune-inflammatory response. The present study describes the specific peripheral immune response related to the different forms of neurocysticercosis in the adult population of both sexes. Asymptomatic cases ( n = 26) mainly presented single calcified cysticerci in brain parenchyma or in the subarachnoid space of the sulci with a predominantly TH2 response (IL-4, IL-5, IL-13), high levels of IL-12 in supernatants of specifically stimulated peripheral blood mononuclear cells, and low plasma levels of all specific IgG subclasses. Symptomatic patients ( n = 26) constituted a heterogeneous group, and had single or multiple cysticerci in vesicular, colloidal, calcified or mixed stages. This group showed parasites located in the subarachnoid space of the base and/or in the sulci, in the ventricular cavities, in parenchyma or in mixed locations. Symptomatic patients showed a depressed specific cellular immune response and increased levels of all specific IgG subclasses. This evidence supports the existence of two clear different immune profiles according to neurocysticercosis that is asymptomatic or symptomatic.