Pyruvate metabolism controls chromatin remodeling during CD4+ T cell activation.

Upon antigen-specific T cell receptor (TCR) engagement, human CD4+ T cells proliferate and differentiate, a process associated with rapid transcriptional changes and metabolic reprogramming. Here, we show that the generation of extramitochondrial pyruvate is an important step for acetyl-CoA production and subsequent H3K27ac-mediated remodeling of histone acetylation. Histone modification, transcriptomic, and carbon tracing analyses of pyruvate dehydrogenase (PDH)-deficient T cells show PDH-dependent acetyl-CoA generation as a rate-limiting step during T activation. Furthermore, T cell activation results in the nuclear translocation of PDH and its association with both the p300 acetyltransferase and histone H3K27ac. These data support the tight integration of metabolic and histone-modifying enzymes, allowing metabolic reprogramming to fuel CD4+ T cell activation. Targeting this pathway may provide a therapeutic approach to specifically regulate antigen-driven T cell activation.

Loss of thymic function promotes EAE relapse in anti-CD52-treated mice.

Anti-CD52 treatment creates a long-lasting CD4 T cell lymphopenia and reduces multiple sclerosis (MS) relapses in humans. In contrast, anti-CD52 therapy at disease onset more fully suppresses experimental autoimmune encephalomyelitis (EAE) in mice, and T cell repopulation is rapid. To test whether prolonged T cell lymphopenia promotes relapses, we thymectomized mice prior to EAE induction and anti-CD52 treatment. Thymectomy greatly reduced the number of recent thymic emigrant T cells and was associated with a prolonged reduction in CD4 T cells in peripheral blood. Two-thirds of thymectomized C57BL/6 mice had an EAE relapse post anti-CD52 treatment, while no surgery and sham surgery euthymic controls remained relapse-free. These data demonstrate that thymus function can alter the effectiveness of anti-CD52 treatment.

A Survey of prevalence of serum antibodies to human immunodeficiency deficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among blood donors.

BACKGROUND: It is a well known fact that HIV, HBV and HCV are global infectious pathogens contributing to mortality and morbidity in all ages thereby making them infections of grievous public health importance. As donor's potend a possible risk of transfusing these infections of global importance, it makes it imperative for the screening of blood and blood products for these pathogens. AIM: This study aims at determining the seroprevalence of HIV, HBV and HCV among intending blood donors. SUBJECTS AND METHODS: A retrospective data analysis for seroprevalence of antibodies to HIV, HBV and HCV was carried out between the 2(nd) of January and 15(th) of June 2010 among intending blood donors aged 18-45 and the association of these infections with age group and blood group were analyzed. Sterile venous anticoagulated blood was collected from each of the donors and analyzed for HIV, HBV and HCV using highly sensitive and specific kits. All the positive samples for HIV- 1/2 were sent for reconfirmation using polymerase chain reaction. RESULTS: Of the 427 samples analyzed, 203 were positive for HIV, 200 for HBV and 24 for HCV, representing a prevalence of 47.54%, 46.83% and 5.71% respectively among intending blood donors. Among them, blood group O "positive" was the most common blood group with 59.25% followed by blood group B "positive", A "positive" and O "negative" respectively (p<0.001). The analysis of relationship showed a tendency of high association of these infections in subjects with O "positive" blood group. CONCLUSION: This study emphasizes the need for proper screening of blood donors for HIV, HBV and HCV.

Survival of Treponema pallidum in banked blood for prevention of Syphilis transmission.

BACKGROUND: Every year, millions of people are exposed to avoidable, life-threatening risks through the trans-fusion of unsafe blood. AIM: To determine the survival time of Treponema pallidum in banked donor blood. MATERIAL AND METHODS: Two groups of male Wistar rats (group A and B) were inoculated intratesticularly with 0.5ml of artificially infected donor blood (final density of Nichols treponemes: 5×10(5) /ml) stored at 4°C for various periods of time. In group A, a pair each of the rats was injected every 12 hours, starting at 0 hr, up to a maximal storage time of 96 hr. In group B, the rats were injected after 72, 120, 192 and 336 hours of storage of the treponemes-blood mixture. Group C which is a control group was injected with blood only, while group D rats were injected with heat-killed treponemes suspended in blood every 12 hours. The detection of Treponema pallidum IgG/IgM was based on the principle of double antigen sandwich immunoassay, in which purified recombinant antigens are employed sufficiently to identify antibodies to Syphilis. The outcomes of interest included the proportion of Syphilis positive rats and the maximal survival hours of T. pallidum in banked blood. RESULTS: 14 rats (77.8%) out of the 18 rats that were involved in group A developed orchitis and positive serology up to 72 hours of storage time, p<0.05. 2 rats (25%) in group B developed orchitis after 72hrs of storage time. All the 18 rats (100%) in the control group C and D showed neither clinical nor serological changes. CONCLUSION: It was concluded that the survival time of T. pallidum in banked donor blood lies between 72-120hrs in this study. Regardless of blood banking temperature, T. pallidum and other transfusion transmissible infections should be screened for prior to allogeneic transfusion.