Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells

The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (T_SCM) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-T_SCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.     

Protective effect of chronic caffeine intake on gene expression of brain derived neurotrophic factor signaling and the immunoreactivity of glial fibrillary acidic protein and Ki-67 in Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive degeneration of the hippocampal and cortical neurons. This study was designed to demonstrate the protective effect of caffeine on gene expression of brain derived neurotrophic factor (BDNF) and its receptor neural receptor protein-tyrosine kinase-β (TrkB) as well as glial fibrillary acidic protein (GFAP) and Ki-67 immunoreactivity in Aluminum chloride (AlCl₃) induced animal model of AD. Fifty adult rats included in this study were classified into 5 group (10 rats each); negative and positive control groups (I&II), AD model group (III), group treated with caffeine from the start of AD induction (IV) and group treated with caffeine two weeks before AD induction (V). Hippocampal tissue BDNF and its receptor (TrkB) gene expression by real time RT-PCR in addition to immunohistochemical study of GFAP and Ki67 immunoreactivity were performed for all rats in the study. The results of this study revealed that caffeine has protective effect through improving the histological and immunohistochemical findings induced by AlCl₃ as well as BDNF and its receptor gene expression. It could be concluded from the current study, that chronic caffeine consumption in a dose of 1.5 mg/kg body weight daily has a potentially good protective effect against AD.     

Organ Donation and Transplantation in Migrants: Piedmont Reality From 2004 To 2011

Background

Over the last 20 years, an increasing number of people have immigrated into Italy. On January 1, 2011, there were 4,570,317 foreign residents in Italy, including 398,910 in the Piedmont region (Italian National Statistics Institute data). The Romanian community was the largest, followed by the Moroccan and Albanian ones. The numbers are even layer if we consider illegal immigrants. As a result, the number of foreign people with brain death has increased, as well as the number of foreign people needing organ transplantations.

Methods

The Piedmont Regional Coordination Agency of Tissue and Organ Procurement has analyzed our 1781 brain death situations between January 2004 and December 2011, including 126 (7%) in people not born in Italy (migrants).

Results

Non-refusal for donation occurred in 79 cases (62.7%). The agency also analyzed each community looking at number of brain deaths and non-refusals of donation. We utilized 61 donors, for 174 transplantations. Migrants in Italy are not only potential tissue and organ donors, but also potential tissue and organ recipients. Between 2004 and 2011, 222 patients who had not been born in Italy had been transplanted with: a liver (n = 66), a kidney (n = 130), a heart (n = 21) or a lung (n = 5).