Treg Heterogeneity, Function, and Homeostasis

Shevyrev, Daniil; Tereshchenko, Valeriy

doi:10.3389/fimmu.2019.03100

Cited by 293 publications

(312 citation statements)

References 128 publications

(139 reference statements)

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“…The expansive level of Treg TCR β chain CDR3 repertoire can directly reflect the immune response of T cells and can also be used for the immune reconstruction after antiviral treatment or bone marrow transplantation, as well as the detection of autoimmune diseases, including biomarkers for the treatment of type I diabetes ( Kern et al, 2014 ; Shevyrev and Tereshchenko, 2019 ). The expansive level of each clonotype in intestine ( Figure 3B ) were conducted, GF mice was mainly in medium frequency (1–2%), while the CL and SPF mice were mainly in high frequency (>2%).…”

Section: Resultsmentioning

confidence: 99%

Heterogeneity of CD4+CD25+Foxp3+Treg TCR β CDR3 Repertoire Based on the Differences of Symbiotic Microorganisms in the Gut of Mice

Xue

Ma³

et al. 2020

Front. Cell Dev. Biol.

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Gut microbes play a crucial role in the occurrence and development of autoimmune diseases. The diversity of intestinal microorganisms affected by the living environment, regulate the immune function of peripheral immune organs and local tissues. In the study, the diversity of intestinal microorganisms of Germ-free (GF), Specific Pathogen-free (SPF), and Clean (CL) BALB/c mice were conducted by 16S rDNA sequencing. High-throughput sequencing technology was used to analysis the composition and characterization of TCR β chain CDR3 repertoires in Regulatory T cells (Treg) in intestine and spleen of GF, SPF, and CL mice, so as to investigate the effects of differential composition of intestinal microorganisms on the CD4 + CD25 + Foxp3 + Treg TCR β CDR3 repertoire of intestine and spleen. We observed that GF, SPF, and CL mice have different gut microorganism composition, and the abundance and quantity of microorganisms are positively correlated with the level of feeding environment. Interestingly, incomplete structure of spleen and small intestine in GF mice was found. Moreover, a significant difference in the usage of high frequency unique CDR3 amino acid sequences was detected in the intestinal Treg TCRβ CDR3 repertoire among GF, SPF and CL mice, and there were a greater heterogeneity in the usage frequency of TRBV, TRBJ , and TRBV-TRBJ combinations gene segments. However, the effect of different feeding environment on the mice Treg TCRβ CDR3 repertoire of spleen was weak, implying that the different composition of intestinal microbiota may primarily affect the diversity of the local Treg TCRβ CDR3 repertoire and does not alter the overall properties of the circulating immune system. These results provide basic data to further analyze the mechanism of gut microbes regulating the intestinal mucosal immune system.

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Section: Resultsmentioning

confidence: 99%

Heterogeneity of CD4+CD25+Foxp3+Treg TCR β CDR3 Repertoire Based on the Differences of Symbiotic Microorganisms in the Gut of Mice

Xue

Ma³

et al. 2020

Front. Cell Dev. Biol.

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“…But when the first barrier is overcome, the second line defense is defective due to the attenuation of cell mediated Th1 immunity and the physiological shift to a Th2 dominant environment which contributes to an overall increased infectious morbidity from intracellular pathogens [ 13 ]. In addition, the enhanced function of T regulatory lymphocytes (Treg), that are usually implicated in the maintenance of maternal immunological tolerance and in pregnancy implantation, further contributes to this Th1/Th2 shift by suppressing Th1 and Th-17 immunity [ 14 ].…”

mentioning

confidence: 99%

Sars-CoV-2 in pregnancy: Why is it better than expected?

Ghi

Pasquo

Mékinian

et al. 2020

European Journal of Obstetrics & Gynecology and Reproductiv

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Since the outbreak of Coronavirus disease in December 2019, information specific to pregnancy remains limited and controversial. Based on data from previous reports, it has been noticed that contrary to prior pandemics such as SARS, MERS and H1N1 and although pregnancy is usually considered as a condition of high susceptibility to viral infections, new SARS-CoV2 infection seems to have a more benign clinical course when affecting pregnant women. We speculate that during pregnancy the physiological “silencing” of the Th1 pro-inflammatory response may blunt the cytokines storm which is thought to play a key-role in the pathogenesis of the severe complications of Covid-19.

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“…Variations in Treg yield across the three donors were observed but are to be expected and may be partially attributed to the degree of hypomethylation occurring in the promoter Treg-specific demethylated region of the master transcriptional factor FOXP3 gene, which is known to vary greatly among individuals (e.g., from 3.6% to 21.3%) 32 – 34 . It is also well accepted that the pool of human FoxP3 + Tregs is heterogeneous and is dependent on different development conditions, anatomical locations, cytokine microenvironment, levels of transcription factors, mechanisms of suppression, surface biomarkers, and age of the individual 35 – 38 . Harvested Tregs from both flasks and Quantum systems maintained a CD4 + CD25 + FoxP3 + Treg phenotype and memory CD4 + CD25 + FoxP3 + CD45RO + Treg phenotype considered important for maintenance of immune homeostasis 39 – 42 with very high frequencies of these phenotypes at harvest.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of Automated Perfusion- and Manual Diffusion-Based Human Regulatory T Cell Expansion and Functionality Using a Soluble Activator Complex

et al. 2020

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Absence or reduced frequency of human regulatory T cells (Tregs) can limit the control of inflammatory responses, autoimmunity, and the success of transplant engraftment. Clinical studies indicate that use of Tregs as immunotherapeutics would require billions of cells per dose. The Quantum® Cell Expansion System (Quantum system) is a hollow-fiber bioreactor that has previously been used to grow billions of functional T cells in a short timeframe, 8–9 d. Here we evaluated expansion of selected Tregs in the Quantum system using a soluble activator to compare the effects of automated perfusion with manual diffusion-based culture in flasks. Treg CD4+CD25+ cells from three healthy donors, isolated via column-free immunomagnetic negative/positive selection, were grown under static conditions and subsequently seeded into Quantum system bioreactors and into T225 control flasks in an identical culture volume of PRIME-XV XSFM medium with interleukin-2, for a 9-d expansion using a soluble anti-CD3/CD28/CD2 monoclonal antibody activator complex. Treg harvests from three parallel expansions produced a mean of 3.95 × 108 (range 1.92 × 108 to 5.58 × 108) Tregs in flasks (mean viability 71.3%) versus 7.00 × 109 (range 3.57 × 109 to 13.00 × 109) Tregs in the Quantum system (mean viability 91.8%), demonstrating a mean 17.7-fold increase in Treg yield for the Quantum system over that obtained in flasks. The two culture processes gave rise to cells with a memory Treg CD4+CD25+FoxP3+CD45RO+ phenotype of 93.7% for flasks versus 97.7% for the Quantum system. Tregs from the Quantum system demonstrated an 8-fold greater interleukin-10 stimulation index than cells from flask culture following restimulation. Quantum system–expanded Tregs proliferated, maintained their antigenic phenotype, and suppressed effector immune cells after cryopreservation. We conclude that an automated perfusion bioreactor can support the scale-up expansion of functional Tregs more efficiently than diffusion-based flask culture.

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Treg Heterogeneity, Function, and Homeostasis

Cited by 293 publications

References 128 publications

Heterogeneity of CD4+CD25+Foxp3+Treg TCR β CDR3 Repertoire Based on the Differences of Symbiotic Microorganisms in the Gut of Mice

Heterogeneity of CD4+CD25+Foxp3+Treg TCR β CDR3 Repertoire Based on the Differences of Symbiotic Microorganisms in the Gut of Mice

Sars-CoV-2 in pregnancy: Why is it better than expected?

A Comparison of Automated Perfusion- and Manual Diffusion-Based Human Regulatory T Cell Expansion and Functionality Using a Soluble Activator Complex

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