Impact of various culture conditions on ex vivo expansion of polyclonal T cells for adoptive immunotherapy

Currently, adoptive immunotherapy is considered as one of the leading treatments in cancer. Successful adoptive immunotherapy depends on producing large numbers of desired T cells ex vivo for infusion. This requires an effective protocol for maximum functional T‐cell expansion while keeping the time and costs to a minimum. Current T‐cell expansion protocols are diverse in their methodology, and a universal protocol of expansion is wanting. Also, new findings regarding T‐cell biology, signaling, and activation have reshaped the strategies of T‐cell propagation over the years, introducing new ways to expand T cells. Here, we reviewed different conditions for blood‐derived polyclonal T‐cell expansion so as to elucidate the influential factors of T‐cell expansion and their efficacy.     

Brain activation during the voiding phase of micturition in healthy adults: A meta‐analysis of neuroimaging studies

Several studies have used a variety of neuroimaging techniques to measure brain activity during the voiding phase of micturition. However, there is a lack of consensus on which regions of the brain are activated during voiding. The aim of this meta‐analysis is to identify the brain regions that are consistently activated during voiding in healthy adults across different studies. We searched the literature for neuroimaging studies that reported brain co‐ordinates that were activated during voiding. We excluded studies that reported co‐ordinates only for bladder filling, during pelvic floor contraction only, and studies that focused on abnormal bladder states such as the neurogenic bladder. We used the activation‐likelihood estimation (ALE) approach to create a statistical map of the brain and identify the brain co‐ordinates that were activated across different studies. We identified nine studies that reported brain activation during the task of voiding in 91 healthy subjects. Together, these studies reported 117 foci for ALE analysis. Our ALE map yielded six clusters of activation in the pons, cerebellum, insula, anterior cingulate cortex (ACC), thalamus, and the inferior frontal gyrus. Regions of the brain involved in executive control (frontal cortex), interoception (ACC, insula), motor control (cerebellum, thalamus), and brainstem (pons) are involved in micturition. This analysis provides insight into the supraspinal control of voiding in healthy adults and provides a framework to understand dysfunctional voiding. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc.     

Effect of single‐dose injection of vitamin D on immune cytokines in ulcerative colitis patients: a randomized placebo‐controlled trial

Ulcerative colitis (UC) is a chronic recurrent inflammation of the colon. It has been proposed that the UC pathogenesis may be related to vitamin D deficiency and/or vitamin D administration in UC patients may have an ameliorating effect on the intestinal inflammation. The aim of this study was to assess the effect of vitamin D on the serum levels of immune cytokines in UC patients. In this double‐blind randomized controlled trial, 90 mild‐to‐moderate UC patients were assigned to get either a single muscular injection of 7.5 mg vitamin D3 or 1 mL normal saline as placebo. Three months later serum levels of IL‐4, IL‐10, IL‐12p70, IFN‐γ, and TNF‐α were measured. Two group variables were compared using independent t‐test and analysis of covariance (ANCOVA). There was a significant increase in vitamin D only in the vitamin D group. Compared to placebo, vitamin D had significant decreasing effects on serum TNF‐α, IFN‐γ, and IL12p70 levels, but it had no significant effect on serum levels of IL4 and IL10. Vitamin D seems to inhibit Th1 immune responses and have no effect on Th2 responses. The findings of this study support several in vitro studies, which suggest a therapeutic immunomodulatory potential of vitamin D.     

Induction of specific cell‐mediated immune responses and protection in BALB/c mice by vaccination with outer membrane vesicles from a Brucella melitensis human isolate

Brucellosis is a worldwide bacterial zoonosis caused by Brucella spp. No approved vaccine is available for human use against the disease. In this study, outer membrane vesicles (OMVs) from a Brucella melitensis biovar 1 human isolate obtained in Iran were used to immunize BALB/c mice (n = 12) by 2 intramuscular injections with a 2‐week interval. Another group of 12 mice was used as non‐vaccinated controls. Two weeks after the last vaccination, six mice of each group were sacrificed, and proliferation and interferon gamma (IFNγ) production responses of their splenocytes were evaluated following in vitro stimulation with killed Brucella cells. The other mice were challenged with the virulent B. melitensis isolate. Two weeks later, mice were killed and spleens were cultured to determine the number of the challenge strain. The results showed proliferative response and IFNγ production of splenocytes from vaccinated mice (stimulation index: 2.18 ± 0.57, and 1519.35 ± 10.70 pg/mL, respectively) were significantly higher than those of control mice (stimulation index: 1.02 ± 0.02, and 210.01 ± 17.58 pg/mL, respectively). Numbers of the challenge strain in spleens of vaccinated mice were also significantly less than those in the controls with 1.6 units of protection. Our study revealed vaccination with OMVs of the B. melitensis isolate could induce specific immune responses and protection against infection in the mouse model suggesting their potential application for active immunization against brucellosis.     

Platelets are important for the development of immune tolerance: Possible involvement of TGF‐β in the mechanism

Platelets have diverse roles in immune processes in addition to their key functions in haemostasis and thrombosis. Some studies imply that platelets may be possibly related to the immune tolerance induction. However, the role of platelets in the development of immune tolerance is not fully understood. The purpose of this study was to investigate the role of platelets in the development of regulatory mechanisms responsible for cutaneous inflammation using a mouse model of low zone tolerance (LZT). Mice were treated with 2,4,6‐trinitro‐1‐chlorobenzene (TNCB) 8 times every other day for tolerance induction with administration of anti‐platelet antibody or control antibody during the tolerance induction phase every 3 days. After the treatment for the tolerance induction, mice were sensitized and then challenged with TNCB. The contact hypersensitivity (CHS) was significantly decreased at 24 hours after challenge in the mice with LZT than in those without LZT. Platelet depletion via administration of anti‐platelet antibody reversed the inhibition of CHS and reduced the frequency of Foxp3⁺ Tregs in the inflamed skin and draining lymph nodes in mice with LZT. In addition, repeated low‐dose skin exposure resulted in elevated plasma levels of transforming growth factor (TGF)‐β1. Interestingly, platelet depletion reduced plasma TGF‐β1 levels of mice with LZT. Furthermore, the CHS response was reduced by administration of recombinant TGF‐β1 during platelet depletion in mice with LZT. Administration of anti‐TGF‐β antibody reversed the inhibition of the CHS responses. These results suggest that platelets are involved in the induction of immune tolerance via the release of TGF‐β1.