HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial.

Importance: Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited.

Objective: To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity.

Design, Setting, And Participants: In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014.

Forensic psychiatric expertise: posttraumatic stress disorder.

Introduction: This article presents our experiences in the field of forensic post-traumatic stress disorder (PTSD).

Objective: The study examined parameters of 30 patients with PTSD who were the subject of forensic expertise (PTSDF) and in 30 patients with PTSD who were not (PTSDN).

Methods: Clinical research and the battery of tests (Impact of Event Scale - IES, Mississippi Scale, and list of symptoms of PCL-M) covered a total of 60 male subjects with a verified diagnosis of PTSD.

Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells.

Background: Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases.

Paradoxical arrest in lupus activity in BXSB mice with highly autoreactive T cells.

T cells with high avidity for antigens are thought to mediate more effective immunity against foreign antigens and cause more severe autoimmunity. The impact of T cell receptor (TCR) avidity on the development of lupus has not been investigated. We took advantage of a transgenic mouse strain (designated MTB) that has a diverse T cell population and a globally stronger reactivity to self.

rs660 polymorphism in Ro52 (SSA1; TRIM21) is a marker for age-dependent tolerance induction and efficiency of alloimmunization in sickle cell disease.

Patients with sickle cell disease (SCD) who receive red blood cell (RBC) transfusions have a higher rate of anti-RBC (allo and auto) antibody development than other transfused subjects. We hypothesized that an incidence and/or kinetics of RBC-specific antibody formation in SCD patients is influenced by a linked inheritance of the hemoglobin beta S (HbbetaS) allele and a polymorphism rs660C/T in the neighboring Ro52 gene. We found that 75% of C/T heterozygous and only 30.

Cutting edge: developmental up-regulation of IFN-gamma-inducible lysosomal thiol reductase expression leads to reduced T cell sensitivity and less severe autoimmunity.

Reactivity to self-peptide/MHC complexes is required for selection of the TCR repertoire in the thymus but can also promote autoimmunity. Reduced TCR sensitivity of mature T cells is thought to help control the autoreactivity in peripheral T cells. The molecular basis for reduced sensitivity of peripheral T cells is not known.

Adaptable TCR avidity thresholds for negative selection.

Central tolerance plays a significant role in preventing autoimmune diseases by eliminating T cells with high and intermediate avidity for self. To determine the manner of setting the threshold for deletion, we created a unique transgenic mouse strain with a diverse T cell population and globally increased TCR avidity for self-peptide/MHC complexes. Despite the adaptations aimed at reducing T cell reactivity (reduced TCR levels and increased levels of TCR signaling inhibitor CD5), transgenic mice displayed more severe experimental allergic encephalomyelitis and lupus.

An unexpected functional link between lysosomal thiol reductase and mitochondrial manganese superoxide dismutase.

Gamma interferon-inducible thiol reductase (GILT) is an enzyme involved in the initial steps of antigen processing and presentation. Recently we have shown that GILT is also expressed in mouse T cells, where it exerts an inhibitory role on T cell activation. In this study, we identified mitochondrial manganese superoxide dismutase (SOD2) as one of the key intermediaries affected by GILT expression in fibroblasts.

CD154-stimulated GM-CSF release by vascular smooth muscle cells elicits monocyte activation--role in atherogenesis.

During the early phase of atherosclerosis, T cells and monocytes attach to and migrate through the endothelium into the vessel wall. To provide an insight into the potential cross talk between T cells and smooth muscle cells (SMC) in atherogenesis, we investigated changes in gene expression caused by CD40 ligation in cultured vascular SMC and their consequences for monocyte activation. CD40 expression in human-cultured SMC was induced by 24-h treatment with tumor necrosis factor-alpha plus interferon-gamma followed by 12-h exposure to mouse myeloma cells stably expressing human CD154 or the corresponding control cells.

Interleukin-10 induction of nitric-oxide synthase expression attenuates CD40-mediated interleukin-12 synthesis in human endothelial cells.

Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine in Th1 cell-mediated chronic inflammatory diseases such as, e.g. Crohn's disease.

[Local epidemic of neonatal listeriosis in Upper Austria--report of 20 cases].

In an 8 month period, 20 cases of listeriosis among neonates were seen in the Federal District of Upper Austria. The majority of mothers reported influenza-like symptoms at the end of pregnancy. 19 cases were early-onset-infections, 6 infants developed meningitis.