Function of T regulatory type 1 cells is down-regulated and is associated with the clinical presentation of coronary artery disease

T regulatory type 1 (Tr1) cells can promote tolerance and suppress inflammation. Atherosclerosis may be induced by the proinflammatory activation of cells in the vasculature and the immune system. Hence, we wondered whether defects in Tr1 function were a contributing factor to coronary artery disease (CAD). Data showed that the frequency of IL-10⁺ Tr1 cells was significantly lower in CAD patients than in controls. Compared to healthy controls, Tr1 cells from CAD patients presented lower CTLA-4 but higher PD-1 expression, in addition to lower IL-10 secretion. When co-incubated with Tconv cells, the CD4⁺CD49b⁺LAG-3⁺CD45RO⁺ Tr1 cells presented IL-10-dependent inhibitory effects, and those from CAD patients presented significantly lower suppression capacity than those from healthy controls. Interestingly, the characteristics of Tr1 cells were associated with clinical features of CAD patients. The frequency of Tr1 cells and the IL-10 and LAG-3 expression by Tr1 cells were negatively correlated with the BMI of the CAD patients. In addition, the Tr1 frequency and the LAG-3 and CTLA-4 expression on Tr1 cells were lower in CAD patients with higher numbers of narrowed vessels. Together, these results suggest that in CAD, Tr1 cells present multiple defects, which are associated with the clinical presentation of the disease.     

Long-term presence of angiotensin II type 1 receptor autoantibody reduces aldosterone production by triggering Ca<Superscript>2+</Superscript> overload in H295R cells

Preeclamptic women are reported to have inadequate plasma volume expansion coupled with a suppressed secretion of aldosterone; however, the specific mechanism of preeclampsia remains unclear. We demonstrated that the presence of long-term angiotensin II type 1 receptor autoantibody (AT1-AA) reduces aldosterone production by triggering a Ca²⁺ overload in H295R cells. AT1-AA was discovered in preeclamptic women and reported to activate AT₁R, and consequently elevate intracellular Ca²⁺. We found that AT1-AA significantly prolonged the time of intracellular Ca²⁺ elevation. Besides promoting aldosterone production as a second messenger, Ca²⁺ overload shows a cytotoxic effect. Our data reveals that long-term presence of AT1-AA triggered a Ca²⁺ overload and consequent impairment of aldosterone production, which could be prevented by a PKC inhibitor, Gö 6983, or a calcium channel inhibitor, nifedipine. These findings have clinical significance because AT₁R blockers are not recommended for treatment of preeclampsia due to their potential harm to the fetus. Our findings also emphasize a potential clinical benefit of immunoadsorption or neutralization of AT1-AA in preeclamptic women.     

A humanized TCR retaining authentic specificity and affinity conferred potent anti‐tumour cytotoxicity

The affinity of T‐cell receptor (TCR) determines the efficacy of TCR‐based immunotherapy. By using human leucocyte antigen (HLA)‐A*02 transgenic mice, a TCR was generated previously specific for human tumour testis antigen peptide MAGE‐A3_112–120 (KVAELVHFL) HLA‐A*02 complex. We developed an approach to humanize the murine TCR by replacing the mouse framework with sequences of folding optimized human TCR variable domains for retaining binding affinity. The resultant humanized TCR exhibited higher affinity and conferred better anti‐tumour activity than its parent murine MAGE‐A3 TCR (SRm1). In addition, the affinity of humanized TCR was enhanced further to achieve improved T‐cell activation. Our studies demonstrated that the human TCR variable domain frameworks could provide support for complementarity‐determining regions from a murine TCR, and retain the original binding activity. It could be used as a generic approach of TCR humanization.     

First isolation of Sarcocystis caninum sarcocysts from two domestic dogs (Canis familiaris) from China

Parasitology Research - The presence of Sarcocystis cysts in the muscle tissue of domestic dogs (Canis familiaris), which normally serve as definitive hosts, is unusual and infrequent. Here, S....     

Predictors of the Quality of Life of Informal Carers of Adults on the Autism Spectrum

Journal of Autism and Developmental Disorders - Carers of adults on the autism spectrum often experience high levels of stress, worry, and caregiver burden. There are few studies identifying the...