Glucocorticoid-induced TNF receptor-triggered T cells are key modulators for survival/death of neural stem/progenitor cells induced by ischemic stroke

Increasing evidences show that immune response affects the reparative mechanisms in injured brain. Recently, we have demonstrated that CD4+T cells serve as negative modulators in neurogenesis after stroke, but the mechanistic detail remains unclear. Glucocorticoid-induced tumor necrosis factor (TNF) receptor (GITR), a multifaceted regulator of immunity belonging to the TNF receptor superfamily, is expressed on activated CD4+T cells. Herein, we show, by using a murine model of cortical infarction, that GITR triggering on CD4+T cells increases poststroke inflammation and decreases the number of neural stem/progenitor cells induced by ischemia (iNSPCs). CD4+GITR+T cells were preferentially accumulated at the postischemic cortex, and mice treated with GITR-stimulating antibody augmented poststroke inflammatory responses with enhanced apoptosis of iNSPCs. In contrast, blocking the GITR–GITR ligand (GITRL) interaction by GITR–Fc fusion protein abrogated inflammation and suppressed apoptosis of iNSPCs. Moreover, GITR-stimulated T cells caused apoptosis of the iNSPCs, and administration of GITR-stimulated T cells to poststroke severe combined immunodeficient mice significantly reduced iNSPC number compared with that of non-stimulated T cells. These observations indicate that among the CD4+T cells, GITR+CD4+T cells are major deteriorating modulators of poststroke neurogenesis. This suggests that blockade of the GITR–GITRL interaction may be a novel immune-based therapy in stroke

Restoration of Innate and Adaptive Immune Responses by HCV Viral Inhibition with an Induction Approach Using Natural Interferon-Beta in Chronic Hepatitis C

Chronic hepatitis C (CHC) is a serious medical problem necessitating more effective treatment. This study investigated the hypothesis that an induction approach with nIFN-beta for 24 weeks followed by PEG-IFN-alpha+ribavirin (standard of care: SOC) for 48 weeks (novel combination treatment: NCT) would increase the initial virologic response rate and restore innate and adaptive immune responses in CHC. Seven CHC patients with a high viral load and genotype 1b were treated with NCT. Serum cytokine and chemokine levels were evaluated during NCT. NCT prevented viral escape and breakthrough resulting in persistent viral clearance of HCVRNA. IL-15 was increased at the end of induction therapy in both early virologic responders (EAVRs) and late virologic responders (LAVRs); CXCL-8, CXCL-10, and CCL-4 levels were significantly decreased (<0.05) in EAVR but not in LAVR during NCT, and IL-12 increased significantly (<0.05) and CXCL-8 decreased significantly (<0.05) after the end of NCT in EAVR but not in LAVR. NCT prevented viral breakthrough with viral clearance leading to improvement of innate and adaptive immunity resulting in a sustained virologic response (SVR). NCT (=8) achieved a higher SVR rate than SOC (=8) in difficult-to-treat CHC patients with genotype 1 and high viral loads

A T15-idiotype-positive T suppressor hybridoma does not use the T15 VH gene segment.

The T suppressive factor (TsF) released from a T15-idiotype-positive phosphocholine (PCho)-specific T hybridoma, F18-3-4, which was formed by fusion between BALB/c T cells and BW5147 thymoma, was immunochemically characterized. TsF inhibited the in vitro induction of both IgE and IgG1 antibody responses of 2,4-dinitrophenyl keyhole limpet hemocyanin (DNP-KLH)-primed spleen cells in the presence of PCho-KLH-DNP. TsF had the ability to bind to PCho determinants and possessed T15 idiotype determinants as well as Iad products. However, we were unable to detect either the rearrangement of the T15 VH gene or the presence of T15 VH gene transcripts in hybridomas by DNA and RNA blot hybridization analyses with the T15 VH DNA probe

On designing DNA databases for the storage and retrieval of digital signals

In this paper we propose a procedure for the storage and retrieval of digital signals utilizing DNA. Digital signals are encoded in DNA sequences that satisfy among other constraints the Noise Tolerance Constraint (NTC) that we have previously introduced. NTC takes into account the presence of noise in digital signals by exploiting the annealing between non-perfect complementary sequences. We discuss various issues arising from the development of DNA-based database solutions (i) in vitro (in test tubes, or other materials) for short-term storage and (ii) in vivo (inside organisms) for long-term storage. We discuss the benefits and drawbacks of each scheme and its effects on the codeword design problem and performance. We also propose a new way of constructing the database elements such that a short-term database can be converted into a long term one and vice versa without the need for a re-synthesis. The latter improves efficiency and reduces the cost of a long-term database