scholarly journals Anti-Inflammatory Mechanism of Astragaloside IV in the Recurrence of Asthma: Critical Role of Memory T Cells and OX40/OX40L Signaling Pathway

2021 ◽  
Author(s):  
Qingqing Yang ◽  
Hongying Zhang ◽  
Jing Sun ◽  
Jingcheng Dong ◽  
Lingwen Kong
Keyword(s):  
T Cells ◽  
Inflammatory Response ◽  
Memory T Cells ◽  
Effector T Cells ◽  
Central Memory ◽  
Response Level ◽  
Inflammatory Mechanism ◽  
Before And After ◽  
Memory Cd4 T Cells

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.

scholarly journals The Role of Pre-existing Cross-Reactive Central Memory CD4 T-Cells in Vaccination With Previously Unseen Influenza Strains

2019 ◽  
Vol 10 ◽  
Author(s):  
Mikalai Nienen ◽  
Ulrik Stervbo ◽  
Felix Mölder ◽  
Sviatlana Kaliszczyk ◽  
Leon Kuchenbecker ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Central Memory ◽  
Memory Cd4 T Cells

scholarly journals A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells

Science ◽  
2014 ◽  
Vol 346 (6205) ◽  
pp. 93-98 ◽  
Author(s):  
Norifumi Iijima ◽  
Akiko Iwasaki
Keyword(s):  
T Cells ◽  
Herpes Simplex ◽  
Memory T Cells ◽  
Local Network ◽  
Sexually Transmitted ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
Memory Cd4 T Cells ◽  
Full Protection

CD8 tissue-resident memory T (TRM) cells provide efficient local control of viral infection, but the role of CD4 TRM is less clear. Here, by using parabiotic mice, we show that a preexisting pool of CD4 TRM cells in the genital mucosa was required for full protection from a lethal herpes simplex virus 2 (HSV-2) infection. Chemokines secreted by a local network of macrophages maintained vaginal CD4 TRM in memory lymphocyte clusters (MLCs), independently of circulating memory T cells. CD4 TRM cells within the MLCs were enriched in clones that expanded in response to HSV-2. Our results highlight the need for vaccine strategies that enable establishment of TRM cells for protection from a sexually transmitted virus and provide insights as to how such a pool might be established.

scholarly journals The CCL2 Chemokine Promotes Early Seeding of the Latent HIV Reservoir

2021 ◽  
Author(s):  
Thomas A. Packard ◽  
Roland Schwarzer ◽  
Eytan Herzig ◽  
Deepashri Rao ◽  
Xiaoyu Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Inflammatory Response ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Central Memory ◽  
Humanized Mice ◽  
Hiv Reservoir ◽  
Latent Hiv ◽  
Memory Cd4 T Cells

ABSTRACTHIV infects long-lived CD4 memory T cells establishing a latent viral reservoir that necessitates lifelong anti-retroviral therapy (ART). How this reservoir is formed so swiftly remains unknown. We now show the innate inflammatory response to HIV infection results in CCL2 chemokine release, which can drive recruitment of cells expressing the CCR2 receptor including a subset of central memory CD4 T cells. Supporting a role for the CCL2/CCR2 axis in rapid reservoir formation, we find 1) treatment of humanized mice with anti-CCL2 antibodies during HIV infection decreases reservoir seeding and 2) CCR2/5+ cells from the blood of HIV-infected individuals on long term ART contain significantly more provirus than CCR2/5-negative memory or naïve cells. Together, these studies support a model where the host’s innate inflammatory CCL2 response to HIV infection recruits CCR2/5+ central memory CD4 T cells to zones of virus-associated inflammation likely contributing to rapid formation of the latent HIV reservoir.GRAPHICAL ABSTRACTWhy is the latent HIV reservoir established so early following infection? An innate immune response occurs during acute infection that establishes a “zone of inflammation” (step 1). The CCL2 chemokine is produced in part through IFI16 sensing of HIV DNA in abortively infected cells. CCL2 promotes rapid recruitment of CCR2/5+ memory CD4 T cells (step 2). Many of these cells become productively infected (step 3) and a fraction become latently infected (step 4). Thus, HIV hijacks the host inflammatory response to rapidly establish the latent reservoir. In support of this model, we find HIV reservoir reduction in humanized mice treated with anti-CCL2 antibodies during early infection. Further, we find that CCR2/5+ CD4 T cells harbor a substantial fraction of detectable proviruses in the blood of HIV-infected individuals on long-term suppressive ART.Abstract Figure

scholarly journals Activated, Pro-Inflammatory Th1, Th17, and Memory CD4+ T Cells and B Cells Are Involved in Delayed-Type Hypersensitivity Arthritis (DTHA) Inflammation and Paw Swelling in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Gaoyang Li ◽  
Shrikant Shantilal Kolan ◽  
Shuai Guo ◽  
Katarzyna Marciniak ◽  
Pratibha Kolan ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Delayed Type Hypersensitivity ◽  
Memory Cd4 T Cells ◽  
Draining Lymph Nodes

Delayed-type hypersensitivity arthritis (DTHA) is a recently established experimental model of rheumatoid arthritis (RA) in mice with pharmacological values. Despite an indispensable role of CD4+ T cells in inducing DTHA, a potential role for CD4+ T cell subsets is lacking. Here we have quantified CD4+ subsets during DTHA development and found that levels of activated, pro-inflammatory Th1, Th17, and memory CD4+ T cells in draining lymph nodes were increased with differential dynamic patterns after DTHA induction. Moreover, according to B-cell depletion experiments, it has been suggested that this cell type is not involved in DTHA. We show that DTHA is associated with increased levels of B cells in draining lymph nodes accompanied by increased levels of circulating IgG. Finally, using the anti-rheumatoid agents, methotrexate (MTX) and the anti-inflammatory drug dexamethasone (DEX), we show that MTX and DEX differentially suppressed DTHA-induced paw swelling and inflammation. The effects of MTX and DEX coincided with differential regulation of levels of Th1, Th17, and memory T cells as well as B cells. Our results implicate Th1, Th17, and memory T cells, together with activated B cells, to be involved and required for DTHA-induced paw swelling and inflammation.

Imatinib Mesylate Has a Stage-Specific Inhibitory Role in Generation of CD26highCD8+ Central Memory T Cells in Vitro and in Vivo.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3243-3243
Author(s):  
Kazuaki Yokoyama ◽  
Tokiko Nagamura-Inoue ◽  
Shin Nakayama ◽  
Ikuo Ishige ◽  
Kazuo Ogami ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Central Memory ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Short Term ◽  
Central Memory T Cells

Abstract CD26 is a transmembrane glycoprotein with intrinsic dipeptidyl peptidase IV (DPPIV) activity as well as costimulatory activity of mitotic signals triggered by the CD3/TCR complex. Based on the expression level of CD26, CD4+ and CD8+ T cells can be divided into 3 (high/intermediate/low or negative) subsets. The significance of CD26 has been studied mainly on CD4+ T cells, and CD26highCD4+ T cells are considered to represent effector memory T cells of a typical Th1 phenotype producing IL2 and IFNg. Furthermore, we reported a significant decrease of this subset in CML patients under imatinib therapy in comparison to those under IFNa therapy and normal volunteers. In contrast, the role of each subset of CD8+ T cells has not yet been clarified. Multi-parameter flow cytometry analysis was performed to characterize CD8+ T cells differentially expressing CD26 in combination with intracellular detection of effector molecules such as perforin (P) and granzyme B (Gr). The capacity to secrete effector cytokines such as IFNg following short-term stimulation was also assessed. As a result, according to the expression level of CD26, we could clearly categorize CD8+ T cells as follows: CD26highCD8+ T cells are defined as central memory T cells which has a phenotype of CD45RO+CD28+CD27+ IFNg+Gr−P+/−, CD26intCD8+ T cells as naïve T cells of CD45ROCD28+ CD27+ IFNg−Gr−P−, and CD26lowCD8+ T cells as effector memory/effector T cells of CD45RO−/+ CD28−CD27−IFNg++Gr++P++, respectively. We next investigated the effects of imatinib on 3 distinct subsets during CD8+ T cell differentiation program. Peripheral blood mononuclear cells were primed with anti-CD3/CD28 MAb and subjected to the grading doses of imatinib for short term culture, followed by flow cytometory. CFSE labeling was used for monitoring cell proliferation. Intriguingly, we found that imatinib dose-dependently inhibits activation, cytokine production and proliferation of CD26highCD8+ central memory T cell subsets in a differentiation stage-specific manner. Finally, we compared the absolute number of peripheral blood CD26highCD8+ T cell subsets between 20 patients with CML in imatinib-induced CCR and 20 normal volunteers, clearly indicating a significant decrease of this subset in CML patients (22.30/ml vs 45.60/ml, p<0.01). The present study offers another evidence for immunomodulatory effects of imatinib or the critical role of Abl (-related) kinase in T cell development, and draws special attention to susceptibility to viral infection of CML patients under long-term imatinib therapy. Figure Figure

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