Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Shevyrev, Daniil; Tereshchenko, Valeriy; Блинова, Е. А.; Knauer, Nadezhda; Pashkina, Ekaterina; Сизиков, А. Э.; Козлов, В. А.

doi:10.3390/life11030245

Cited by 7 publications

(8 citation statements)

References 56 publications

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“…Besides, a disturbance of the functional specialization of Treg cells and their conversion into pathogenic Th lymphocytes can occur (154). Some studies showed that Treg cells could not suppress the proliferation of T cells that received a strong TCR signal under the influence of IL-7 and IL-15, which was important in the context of homeostatic proliferation when a strong TCR signal gives advantages to T cells in the competition for the factors of survival (155,156). This fact is interesting taking into account that AD-associated variants of MHCs contribute to a better presentation of antigens associated with the disease, and thus, homeostatic proliferation can contribute to the expansion of self-reactive T-clones in people with genetic predisposition (157,158).…”

Section: Potential Risks Of Immune Disequilibriummentioning

confidence: 99%

Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes

2021

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In this review, we described the structure and organization of antigen-recognizing repertoires of B and T cells from the standpoint of modern immunology. We summarized the latest advances in bioinformatics analysis of sequencing data from T and B cell repertoires and also presented contemporary ideas about the mechanisms of clonal diversity formation at different stages of organism development. At the same time, we focused on the importance of the allelic variants of the HLA genes and spectra of presented antigens for the formation of T-cell receptors (TCR) landscapes. The main idea of this review is that immune equilibrium and proper functioning of immunity are highly dependent on the interaction between the recognition and the presentation landscapes of antigens. Certain changes in these landscapes can occur during life, which can affect the protective function of adaptive immunity. We described some mechanisms associated with these changes, for example, the conversion of effector cells into regulatory cells and vice versa due to the trans-differentiation or bystander effect, changes in the clonal organization of the general TCR repertoire due to homeostatic proliferation or aging, and the background for the altered presentation of some antigens due to SNP mutations of MHC, or the alteration of the presenting antigens due to post-translational modifications. The authors suggest that such alterations can lead to an increase in the risk of the development of oncological and autoimmune diseases and influence the sensitivity of the organism to different infectious agents.

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Section: Potential Risks Of Immune Disequilibriummentioning

confidence: 99%

Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes

2021

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“…At a young age, the index varies around 2.0, and in old age it may decrease below 1.0 [ 28 ]. Simultaneous increases in Th and CTL have been noted in inflammatory diseases and autoimmune disorders [ 29 , 30 ]. In this study, Macaca fascicularis showed a decrease in Th and an increase in CTL.…”

Section: Discussionmentioning

confidence: 99%

Age-Related Changes in the Clustering of Blood Populations in Cynomolgus Monkeys Depend on Sex and Immune Status

Karal-ogly

Shumeev

Keburiya

et al. 2023

Life

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Non-anthropoid primates cynomolgus monkeys (Macaca fascicularis), also known as crab-eating macaques, are increasingly used in biomedical and preclinical studies due to their evolutionary proximity to humans, sharing similar diets, infectious and senile diseases. Age-related changes and sexual dimorphism of the immune system of C. monkeys have not been sufficiently characterized in literature, though age and sex differences affect the course of diseases and sensitivity to medications. Aging in C. monkeys is accompanied by an increase in CD3+CD4+CD8+ (DP-T) cells, plasma B-cells, and a decrease in platelets. Erythromyeloid bias has also been noticed in older animals. There was an increase in eosinophils, haematocrit (HCT) and haemoglobin concentration (HGB). Senile decline in the function of the immune system had sex differences. An increase in the number of monocytes, cytotoxic lymphocytes (CTL) and a decrease in the T-helper population were more pronounced in older females. A significant reduction in the number of B-cells and activated T-cells was detected in males only. A moderate correlation with the regression model of aging was established for DP-T, HCT and HGB. The reduction in the B cells count in males and the increase in CTL level in females are moderately correlated with age. Other blood cell populations did not show significant correlations in the regression models due to their high sample variability. The novel cell population CD3-CD20loCD16/CD56+, presumably NK-cells subset, was revealed. This cell population demonstrated an increase trend with age in both sexes. Population-statistical age norms for different sexes for young and very old macaques were established. The blood population clusters associated with sex and immune status in older animals were also identified.

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“…There were no significant differences in the total number of Treg cells, effector Treg cells, or activated T cells between KD RA and non-KD RA patients, though the Treg cells and effector Treg cells may be functionally different between the two groups. Treg cells have reduced functional activity in vivo , which may lead to the proliferation of various T-cell clones, including self-reactive clones, resulting in reduced TCR diversity and increased risk of autoimmunity ( Shevyrev et al, 2021 ). This study investigated the TCR receptors of Treg cells using high-throughput sequencing and found reduced TCR diversity in Treg cells, which is in agreement with existing findings.…”

Section: Discussionmentioning

confidence: 99%

High-throughput Treg cell receptor sequencing reveals differential immune repertoires in rheumatoid arthritis with kidney deficiency

Zhang

Jiao

Deng

et al. 2023

PeerJ

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Background Regulatory T (Treg) cells are important immune cells that are regulated by adaptive immunity in the composition of Treg-cell subsets and T-cell receptors (TCRs). Treg cells are related to most autoimmune diseases, such as rheumatoid arthritis (RA). In traditional Chinese medicine (TCM), RA is typically attributed to kidney deficiency (KD) associated with the immunosenescence that causes immune dysfunction and the impaired function of Treg cells. So far, however, no mechanism related to KD and immune repertoires has been identified in RA. Methods Flow cytometry and high-throughput Treg-cell receptor sequencing were used to investigate the amount of different Treg-cell subsets and the diversity of TCRs between RA patients and healthy subjects, as well as between KD RA and non-KD RA patients. RT-qPCR was used to validate the high-throughput sequencing results. Results The data showed that the amount of naïve Treg cells in KD patients was less than in non-KD RA patients (P = 0.004) with no significant differences observed between other subsets. In the TCR of Treg cells, the length of complementarity determining region 3 (CDR3) was low and clonotypes increased in the KD group compared with the non-KD group. The diversity and abundance of Treg TCRs were low, as determined by the Hill number. In addition, several V(D)J combinations, such as T-cell receptor beta variable 7-2 (TRBV7-2), TRBV11-1, TRBV13, TRBV15, and TRBJ2-3, varied significantly between the two groups, indicating that KD causes Treg dysfunction. RT-qPCR shows that FOXP3 expression in peripheral blood Treg is lower in KD than in non-KD. Conclusion The results demonstrate the close correlation between KD and immune repertoires in RA and provide a new evaluation method for RA in TCM.

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Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Cited by 7 publications

References 56 publications

Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes

Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes

Age-Related Changes in the Clustering of Blood Populations in Cynomolgus Monkeys Depend on Sex and Immune Status

High-throughput Treg cell receptor sequencing reveals differential immune repertoires in rheumatoid arthritis with kidney deficiency

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