memory cd4 t cells
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2021 ◽  
Author(s):  
Yifei Wang ◽  
Qin Tian ◽  
Yaxing Hao ◽  
Wei Yao ◽  
Jinjin Lu ◽  
...  

Author(s):  
Nan Xiong ◽  
Qiangming Sun

At present, there are still no specific therapeutic drugs and appropriate vaccines for Dengue. Therefore, it is very important to explore distinct clinical diagnostic indicators. In this study, we combined differentially expressed genes (DEGs) analysis and weighted co-expression network analysis (WGCNA) to screen a stable and robust biomarker which can be used to distinguish three clinical stages of Dengue and severity of Dengue. CD38 can distinguish excellently Early Acute, Late Acute, Convalescent stages for Dengue patients, and ZNF595 can discriminate DHF from DF in whole acute stages. We also found that three clinical stages can be discriminated based on the fractions of Plasma cells, activated memory CD4+ T cells, and Monocytes. In different clinical stages different immune cells function positively. Negative inhibition of viral replication based on Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA), up-regulated autophagy genes and impairing immune system are potential reasons resulting in dengue hemorrhagic fever (DHF).


2021 ◽  
Author(s):  
Qingqing Yang ◽  
Hongying Zhang ◽  
Jing Sun ◽  
Jingcheng Dong ◽  
Lingwen Kong

Abstract The recurrence of asthma is partly mediated by central memory CD4(+) T cells(TCM) that promote lung inflammation through the production of effector T cells. Targeting the expansion of pathogenic TCM(central memory CD4(+) T cells) is a promising therapeutic strategy to block production of effector T cells. The study aimed to evaluate the regulatory effects of Astragaloside IV (AS-IV) on TCMs and try to explore the anti-inflammatory mechanism of AS-IV in asthmatic mice. We developed a murine model of asthma by ovalbumin(OVA) challenge. Flow cytometry was used to determine the counts of CD4(+) memory T cells subgroups. Pulmonary tests, inflammatory cytokines in blood and inflammatory cells in bronchoalveolar lavage fluid,were measured to evaluate the inflammatory response level before and after AS-IV treatment. To further determine the role of TCM in the recurrence of inflammation, TCM were isolated by Magnetic-activated cell sorting (MACS) from spleens of asthma, control, AS-IV and dexamethasone treatment mice. The isolated cells were adoptive transferred into nude mice via tail intravenous injection, respectively, and the inflammatory response level of the lung was measured after OVA challenge. The effects of AS-IV on TCM viability, the number of the frequency (in percent) of CD44highCD62Lhigh cells, and the expression of OX40 and OX40L were measured before and after AS-IV treatment. In circulation blood, we demonstrated increased percentages of CCR7highCD62LlowCD4+ effector memory T cells(TEM) and decreased CCR7highCD62LhighCD4(+) TCM in asthma mice. On the contrary, the TEM subgroup percentage were decreased and the TCM phenotypes were increased in asthmatic spleen. AS-IV treatment significantly decreased CD4(+) T effector phenotypes in blood and inhibited the lung inflammatory response. Additionally, the inflammation of nude mice that adoptive transferred TCM from AS-IV treatment asthmatic mice had relieved inflammation compared with asthmatic group. In vitro, we successfully used spleen T lymphoid cells stimulated with IL-7 and OVA to induce a central memory T cell model. TCM co-cultured with DC cells had a significantly increased expression of OX40/OX40L. AS-IV pretreatment partially inhibited the expression of OX40 signal pathway. This study indicates that AS-IV can ameliorate asthma inflammation by inhibiting the production of TEM form TCM. The treatment mechanism maybe involved in the OX40/OX40L pathway.


2021 ◽  
Vol 12 ◽  
Author(s):  
Dong Liu ◽  
Meixuan Song ◽  
Fengchuan Jing ◽  
Bin Liu ◽  
Qijian Yi

Kawasaki disease (KD) is a systemic vasculitis that predominantly damages medium- and small-sized vessels, and mainly causes coronary artery lesions (CALs). The diagnostic criterion of KD mainly depends on clinical features, so children could be easily misdiagnosed and could suffer from CALs. Through analysis, a total of 14 immune-related DEGs were obtained, of which IL1B, ADM, PDGFC, and TGFA were identified as diagnostic markers of KD. Compared with the non-KD group, KD patients contained a higher proportion of naive B cells, activated memory CD4 T cells, gamma delta T cells, and neutrophils, while the proportions of memory B cells, CD8 T cells, activated memory CD4 T cells, and activated NK cells were relatively lower. In conclusion, immune-related genes can be used as diagnostic markers of KD, and the difference in immune cells between KD and non-KD might provide new insight into understanding the pathogenesis of KD.


Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1439
Author(s):  
Kevin M. Dennehy ◽  
Eva Löll ◽  
Christine Dhillon ◽  
Johanna-Maria Classen ◽  
Tobias D. Warm ◽  
...  

Memory T-cell responses following infection with coronaviruses are reportedly long-lived and provide long-term protection against severe disease. Whether vaccination induces similar long-lived responses is not yet clear since, to date, there are limited data comparing memory CD4+ T-cell responses induced after SARS-CoV-2 infection versus following vaccination with BioNTech/Pfizer BNT162b2. We compared T-cell immune responses over time after infection or vaccination using ELISpot, and memory CD4+ T-cell responses three months after infection/vaccination using activation-induced marker flow cytometric assays. Levels of cytokine-producing T-cells were remarkably stable between three and twelve months after infection, and were comparable to IFNγ+ and IFNγ+IL-2+ T-cell responses but lower than IL-2+ T-cell responses at three months after vaccination. Consistent with this finding, vaccination and infection elicited comparable levels of SARS-CoV-2 specific CD4+ T-cells after three months in addition to comparable proportions of specific central memory CD4+ T-cells. By contrast, the proportions of specific effector memory CD4+ T-cells were significantly lower, whereas specific effector CD4+ T-cells were higher after infection than after vaccination. Our results suggest that T-cell responses—as measured by cytokine expression—and the frequencies of SARS-CoV-2-specific central memory CD4+T-cells—indicative of the formation of the long-lived memory T-cell compartment—are comparably induced after infection and vaccination.


2021 ◽  
Vol 131 (23) ◽  
Author(s):  
Suzanne L. Campion ◽  
Elena Brenna ◽  
Elaine Thomson ◽  
Will Fischer ◽  
Kristin Ladell ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2398
Author(s):  
Xiaolei Wang ◽  
Widade Ziani ◽  
Ronald S. Veazey ◽  
Huanbin Xu

The HIV reservoir size in target CD4+ T cells during primary infection remains unknown. Here, we sorted peripheral and intestinal CD4+ T cells and quantified the levels of cell-associated SIV RNA and DNA in rhesus macaques within days of SIVmac251 inoculation. As a major target cell of HIV/SIV, CD4+ T cells in both tissues contained a large amount of SIV RNA and DNA at day 8–13 post-SIV infection, in which productive SIV RNA highly correlated with the levels of cell-associated SIV DNA. Memory CD4+ T cells had much higher viral RNA and DNA than naïve subsets, yet memory CD4+ T cells co-expressing CCR5 had no significant reservoir size compared with those that were CCR5-negative in blood and intestine. Collectively, memory CD4+ T cells appear to be the major targets for primary infection, and viral reservoirs are equally distributed in systemic and lymphoid compartments in acutely SIV-infected macaques.


2021 ◽  
Author(s):  
◽  
Marina Catherine Goudie Harvie

<p>The acquisition of protective immunity is a critical feature of the immune system. It is the unique ability of the adaptive immune response to generate and maintain long-lived antigen specific memory cells, which is the key to preventing reinfection and achieving the goal of protective immunity. The importance of secondary lymphoid tissue (such as lymph nodes) as a site of effector CD4 T cell responses and the generation, dissemination and maintenance of memory CD4 T cells is well accepted. However, a key research area needing investigation is the basic biology of the CD4 T cell, particularly the recirculation, distribution and maintenance of CD4 T cells at sites throughout the body. To address these issues we used Nippostrongylus brasiliensis as a model of CD4 mediated protective immunity, combined with G4/IL-4 reporter mice. We show that the lung environment is critical for the priming of CD4 T cells and conferring protective immunity. In contrast to others we find no protective role for the CD4 T cell population of the skin and only a minor role for the population within the gut. In a separate study we used the drug fingolimod (FTY720) to block the cellular trafficking between lymph node and lung tissue during immune responses. Interestingly, our findings show that protection against N. brasiliensis infection is maintained when CD4 T cell recirculation between the lung and lymph node is blocked. Furthermore, we reveal that peripheral lung residing CD4 T cells are sufficient for conferring protective immunity in the N. brasiliensis model, generating support for the model of effector lymphoid tissue. When N. brasiliensis experienced CD4 T cells were localised to the lung by intranasal adoptive transfer they were able to confer protection against infection in otherwise naive animals, as early as 48 hours post infection. The most striking finding of this work is the discovery that memory CD4 T cells residing in the lung that are sufficient to confer protection against reinfection. Identifying the factors in the lung and lymph node that induce and support this CD4 T cell subset will be an important area of future research given its high relevance to the design of vaccines against parasite infections.</p>


2021 ◽  
Author(s):  
◽  
Marina Catherine Goudie Harvie

<p>The acquisition of protective immunity is a critical feature of the immune system. It is the unique ability of the adaptive immune response to generate and maintain long-lived antigen specific memory cells, which is the key to preventing reinfection and achieving the goal of protective immunity. The importance of secondary lymphoid tissue (such as lymph nodes) as a site of effector CD4 T cell responses and the generation, dissemination and maintenance of memory CD4 T cells is well accepted. However, a key research area needing investigation is the basic biology of the CD4 T cell, particularly the recirculation, distribution and maintenance of CD4 T cells at sites throughout the body. To address these issues we used Nippostrongylus brasiliensis as a model of CD4 mediated protective immunity, combined with G4/IL-4 reporter mice. We show that the lung environment is critical for the priming of CD4 T cells and conferring protective immunity. In contrast to others we find no protective role for the CD4 T cell population of the skin and only a minor role for the population within the gut. In a separate study we used the drug fingolimod (FTY720) to block the cellular trafficking between lymph node and lung tissue during immune responses. Interestingly, our findings show that protection against N. brasiliensis infection is maintained when CD4 T cell recirculation between the lung and lymph node is blocked. Furthermore, we reveal that peripheral lung residing CD4 T cells are sufficient for conferring protective immunity in the N. brasiliensis model, generating support for the model of effector lymphoid tissue. When N. brasiliensis experienced CD4 T cells were localised to the lung by intranasal adoptive transfer they were able to confer protection against infection in otherwise naive animals, as early as 48 hours post infection. The most striking finding of this work is the discovery that memory CD4 T cells residing in the lung that are sufficient to confer protection against reinfection. Identifying the factors in the lung and lymph node that induce and support this CD4 T cell subset will be an important area of future research given its high relevance to the design of vaccines against parasite infections.</p>


2021 ◽  
Author(s):  
Jiarong Huang ◽  
Jinxuan Song ◽  
Xiangyu Li ◽  
Shuangfei Liu ◽  
Wentao Huang ◽  
...  

Abstract Background Studies have shown that long noncoding RNAs and N6-methyladenosine play an important role in gastric cancer. The purpose of this study was to determine the correlation and prognostic value of m6A-related lncRNAs and immune infiltration in gastric cancer. Methods We downloaded the clinically related information and RNA-Seq transcriptome data of gastric cancer patients from the TCGA database. Univariate Cox regression analysis and Pearson analysis were used to screen out m6A-related lncRNAs. Consensus cluster analysis was used to divide the sample into two clusters, and LASSO analysis and minimum absolute shrinkage were used to construct a risk scoring model. Results A total of 25 lncRNA expression profiles were screened, and gastric cancer patients were divided into different subtypes. Cluster 2 had a better prognosis, but its matrix score, estimate score and immune score were low. Cluster 1 was rich in resting memory CD4 T cells, regulatory T cells, monocytes, and resting mast cells, and Cluster 2 was rich in activated memory CD4 T cells and follicular helper T cells. Thirteen lncRNAs were selected to construct a risk model, and the prognosis of gastric cancer patients in the high-risk group was poor. The expression of PD-L1 in tumors is significantly higher than that in normal tissues. Univariate and multivariate Cox regression analysis results showed that the overall survival rate was significantly related to stage and risk score, which can be used as an independent prognostic factor. The results of the heat map and scatter plot showed that clusters (P=0.0045) and grade (G1-2, G3, P=0.0037) were significantly related to prognosis. The results of the relationship between the risk score and immune cell infiltration showed that memory B cells, resting dendritic cells, M0 macrophages, and M2 macrophages were positively correlated with risk scores, while resting mast cells, monocytes, activated NK cells, and follicular helper T cells were negatively correlated with risk scores. Conclusion The results of this study indicate that m6A-related lncRNAs may play an important role in the prognosis of gastric cancer patients and the tumor immune microenvironment and provide help for the treatment of gastric cancer patients.


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