Clinical implications of CD4+ T cell subsets in adult atopic asthma patients

Wiest, Matthew; Upchurch, Katherine; Yin, Wu; Ellis, Jerome; Xue, Yaming; Lanier, Bob; Millard, Mark; Joo, Hye Mee; Oh, Sang Kon

doi:10.1186/s13223-018-0231-3

Cited by 17 publications

(19 citation statements)

References 69 publications

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“…There was no effect of sex on omalizumab response in this study. The two groups of patients also maintained similar frequencies of CCR4 + central memory (CM) CD4 + T cells which are known to be resistant to current therapies 5 . There was also no difference in the frequency of regulatory B cell subsets 6 .…”

Section: Figurementioning

confidence: 82%

Obesity influences the outcomes of anti‐IgE (omalizumab) therapy of asthma

Upchurch

Mamaril-Davis

et al. 2020

Clin Experimental Allergy

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Section: Figurementioning

confidence: 82%

Obesity influences the outcomes of anti‐IgE (omalizumab) therapy of asthma

Upchurch

Mamaril-Davis

et al. 2020

Clin Experimental Allergy

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“…Так, в проведенном недавно исследовании, наряду с функциональными изменениями Т-клеток памяти, было выявлено повышенное содержание TcmCD62L + и TemCD62L + в CD4 + клетках периферической крови у пациентов с БА [4]. В другой работе было показано, что у взрослых пациентов с БА, вне зависимости от формы и степени тяжести заболевания, повышается число CD4 + Tcm, но не CD4 + Tem по сравнению с донорами, что не подтверждается данными нашего исследования [28]. На наш взгляд, обнаруженное снижение количества CD4 + и CD8 + CD62L + Tem в периферической крови у пациентов, находящихся в обострении БА может быть свидетельством того, что активированные Тem мигрируют на периферию в стадии обострения БА и находятся преимущественно в дыхательных путях в виде резидентных Тem.…”

Section: Discussionunclassified

CONTENTS OF CD4<sup>+</sup> AND CD8<sup>+</sup> EFFECTOR MEMORY CELLS AND PROLIFERATIVE ACTIVITY OF T LYMPHOCYTES IN BRONCHIAL ASTHMA

et al. 2019

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Bronchial asthma is a chronic inflammatory disease of the respiratory tract. T-lymphocytes play a key role in pathogenesis of this allergic disease. The reduction in number of naïve T cells and the accumulation of memory T cells in bronchial asthma are accompanied by dysregulation of T lymphocyte function. In present study, we have investigated the contents of different T lymphocyte subpopulations in peripheral blood as well as in resting and PHA-stimulated cultures, along with their proliferative capacity in patients with bronchial asthma and healthy donors. The study included 10 patients with bronchial asthma (age 45.4±11.8 years). One-half of patients was in remission state, the others having been at the stage of clinical exacerbation. The group of donors was formed by healthy individuals matched by gender and age to the patients. Based on expression of cell surface markers CD45R0, CD62L and CD197 (CCR7), the CD4+ and CD8+T lymphocytes were divided into central (Tcm) and effector memory cells (Tem), naïve T lymphocytes (Tnaïve) and terminally differentiated effector cells (Temra) using flow cytometry technique. The proliferative activity of Tcm, Tem and Tnaïve was evaluated in response to PHA as a functional marker of T cells. We have found that the percentage of peripheral CD4+TemCD62L+ and CD8+TemCD62L+ cells in the patients with asthma exacerbation was significantly reduced, if compared to the donors. Following PHA stimulation, these differences in T cell subsets between the groups of patients and donors were not detectable. We performed a correlation analysis between the memory T cell contents and age of the subjects studied. It was shown that the relative amounts of CD4+ and CD8+ memory cells increased with age in asthmatics, but not in healthy donors. Analysis of mitogen-induced proliferation showed that Tcm and Tnaïve cells proliferated more actively than other subpopulations in both groups. Meanwhile, the proliferative activity of CD4+T lymphocytes and subsets of CD8+Tcm, CD4+Tcm and CD4+Tem62L was higher in the group of asthma patients in remission state than in the patients with exacerbating disease, and healthy donors. The revealed increase in the relative number of memory T cells with age suggests that these cells participate in development of bronchial asthma. Proliferative response of the studied subpopulations, which was comparable to the donor values, suggests a functional maintenance of memory T cells and naïve T lymphocytes in bronchial asthma. The increased proliferation of some T-cell subpopulations in asthmatics in remission suggests an activated state of memory T cells. The observed decrease in the number of CD4+TemCD62L+ and CD8+TemCD62L+ in patients with asthma exacerbation may be, by our opinion, associated with an active inflammatory process in the airways.

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“…T CM s display core molecular signatures and functional attribute characteristics of stem cells[18], however, current common asthma therapeutics, including corticosteroids, can not block T CM s differentiating in T EM [19,20]. In this study, we explored the treatment mechanism of AS-IV in the regulation of proliferation of T CM s.…”

Section: Introductionmentioning

confidence: 99%

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

Yang

Zhang

Sun

et al. 2021

Preprint

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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.

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Clinical implications of CD4+ T cell subsets in adult atopic asthma patients

Cited by 17 publications

References 69 publications

Obesity influences the outcomes of anti‐IgE (omalizumab) therapy of asthma

Obesity influences the outcomes of anti‐IgE (omalizumab) therapy of asthma

CONTENTS OF CD4<sup>+</sup> AND CD8<sup>+</sup> EFFECTOR MEMORY CELLS AND PROLIFERATIVE ACTIVITY OF T LYMPHOCYTES IN BRONCHIAL ASTHMA

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

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