During chronic viral infection, virus-specific CD8(+) T cells become exhausted, exhibit poor effector function and lose memory potential. However, exhausted CD8(+) T cells can still contain viral replication in chronic infections, although the mechanism of this containment is largely unknown. Here we show that a subset of exhausted CD8(+) T cells expressing the chemokine receptor CXCR5 has a critical role in the control of viral replication in mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV). These CXCR5(+) CD8(+) T cells were able to migrate into B-cell follicles, expressed lower levels of inhibitory receptors and exhibited more potent cytotoxicity than the CXCR5(-) [corrected] subset. Furthermore, we identified the Id2-E2A signalling axis as an important regulator of the generation of this subset. In patients with HIV, we also identified a virus-specific CXCR5(+) CD8(+) T-cell subset, and its number was inversely correlated with viral load. The CXCR5(+) subset showed greater therapeutic potential than the CXCR5(-) [corrected] subset when adoptively transferred to chronically infected mice, and exhibited synergistic reduction of viral load when combined with anti-PD-L1 treatment. This study defines a unique subset of exhausted CD8(+) T cells that has a pivotal role in the control of viral replication during chronic viral infection.

Impaired immunity in late stage cancer patients is not limited to anti-tumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection 1 – 3 . This has been largely attributed to chemotherapy-induced impairment of innate immunity such as neutropenia 2 , whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8 + T cell responses against pathogens in treatment-naïve mice bearing large tumors. Specifically, we identify CD45 + erythroid progenitor cells (CD71 + TER119 + , EPCs) as robust immunosuppressors. CD45 + EPCs, induced by tumor growth-associated extramedullary hematopoiesis, accumulate in the spleen to become a major population, outnumbering regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). The CD45 + EPC transcriptome closely resembles that of MDSCs, and, like MDSCs, reactive oxygen species production is a major mechanism underlying CD45 + EPC-mediated immunosuppression. Similarly, an immunosuppressive CD45 + EPC population was detected in cancer patients with anemia. These findings identify a major population of immunosuppressive cells that likely contributes to the impaired T cell responses commonly observed in advanced cancer patients.

The ultimate goal of phototherapy based on nanoparticles, such as photothermal therapy (PTT) which generates heat and photodynamic therapy (PDT) which not only generates reactive oxygen species (ROS) but also induces a variety of anti-tumor immunity, is to kill tumors. In addition, due to strong efficacy in clinical treatment with minimal invasion and negligible side effects, it has received extensive attention and research in recent years. In this paper, the generations of nanomaterials in PTT and PDT are described separately. In clinical application, according to the different combination pathway of nanoparticles, it can be used to treat different diseases such as tumors, melanoma, rheumatoid and so on. In this paper, the mechanism of pathological treatment is described in detail in terms of inducing apoptosis of cancer cells by ROS produced by PDT, immunogenic cell death to provoke the maturation of dendritic cells, which in turn activate production of CD4+ T cells, CD8+T cells and memory T cells, as well as inhibiting heat shock protein (HSPs), STAT3 signal pathway and so on.

Maize is a major crop whose rich genetic diversity provides an advanced resource for genetic research. However, a tool for rapid transient gene function analysis in maize that may be utilized in most maize cultivars has been lacking, resulting in reliance on time-consuming stable transformation and mutation studies to obtain answers. We developed an efficient virus-induced gene silencing (VIGS) vector for maize based on a naturally maize-infecting cucumber mosaic virus (CMV) strain, ZMBJ-CMV. An infectious clone of ZMBJ-CMV was constructed, and a vascular puncture inoculation method utilizing Agrobacterium was optimized to improve its utility for CMV infection of maize. ZMBJ-CMV was then modified to function as a VIGS vector. The ZMBJ-CMV vector induced mild to moderate symptoms in many maize lines, making it useful for gene function studies in critically important maize cultivars, such as the sequenced reference inbred line B73. Using this CMV VIGS system, expression of two endogenous genes, ZmPDS and ZmIspH, was found to be decreased by 75% and 78%, respectively, compared with non-silenced tissue. Inserts with lengths of 100-300 bp produced the most complete transcriptional and visual silencing phenotypes. Moreover, genes related to autophagy, ZmATG3 and ZmATG8a, were also silenced, and it was found that they function in leaf starch degradation. These results indicate that our ZMBJ-CMV VIGS vector provides a tool for rapid and efficient gene function studies in maize.

Ketogenic diet (KD) is a high-fat, low-protein and low-carbohydrate diet. It is reported that KD can provide the neuroprotection for the neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease (PD) and amyotrophic lateral sclerosis. The main clinical symptom of PD is motor dysfunction derived from the loss of dopaminergic neurons in the substantia nigra (SN) and dopamine content in the striatum subsequently. It is well known that treatments with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice produce motor dysfunction, biochemical, and neurochemical changes remarkably similar to idiopathic PD patients. In this study, we investigated the neuroprotective and anti-inflammatory effects of KD in MPTP-treated mice. The data showed that pretreatment with KD alleviated the motor dysfunction induced by MPTP. The decrease of Nissl-staining and tyrosine hydroxylase (TH)-positive neurons induced by MPTP was inhibited in the SN. The change of dopamine was very similar to dopaminergic neurons in the SN. KD inhibited the activation of microglia induced by MPTP in the SN. The levels of proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) in the SN were also decreased and induced by MPTP. So, we concluded that KD was neuroprotective and anti-inflammatory against MPTP-neurotoxicity.