Changes in peripheral blood regulatory T cells, and IL−6 and IL−10 levels predict response of pediatric medulloblastoma and germ cell tumors with residual or disseminated disease to craniospinal irradiation

Abstract OBJECTIVE This study was designed to retrospectively analyze the dynamic changes of peripheral blood lymphocyte subsets and prognosis among patients with intracranial germ cell tumors. METHODS A total of 150 intracranial germ cell tumors patients diagnosed between June 2011 till November 2019 were retrospectively investigated. Peripheral blood total T lymphocytes (CD3+) percentage, T helper/inducible lymphocytes(CD3+CD4+)percentage, T inhibitory/toxic lymphocytes (CD3+CD8+) percentage, B lymphocyte (CD19+) percentage, NK lymphocyte (CD3/CD16+CD56+) percentage, regulatory T cells (CD4+CD25+,CD8+CD25+), and T helper/toxic lymphocyte ratio (CD4+/CD8+ ratio) were quantified by flow cytometry analysis. Clinical information was extracted from the database in Sun Yat-sen University Cancer Center and survival data was confirmed through outpatient visits and telephone follow-up. RESULTS T lymphocytes population was increased after anti-tumor treatment, with significant difference of total T lymphocytes (CD3+), inhibitory/toxic T cells (CD3+CD8+) and regulatory T cells (CD4+CD25+ and CD8+CD25+), (p=0.008, p=0.000, p=0.008 and p=0.001 respectively), while B lymphocytes(CD19+) decreased after chemotherapy(p=0.003). The dynamic levels of T lymphocyte and B lymphocyte subpopulation after chemotherapy did not present significant differences between gender, age, and locations of tumors (p >0.05), except CD4+CD25+ T cells in younger children (age< 16 years older) increased significantly than the elder (age >16), p=0.04. Patients with increased CD19+ B cells presented significant suboptimal outcomes compared with the no increased (p=0.024). Similarly, increased CD3+ T cells, CD3+CD8+ T cells, CD4+CD25+ T cells reduced the risk of death (p=0.006, p=0.019, p=0.042 respectively). Multivariate Cox Regression analysis showed: increased CD19+ B cells, p=0.04, HR=1.688, 95%CI=1.025-2.779. CONCLUSION After anti-tumor treatment, cell-mediated immunity activated, enhanced, and dominated in anti-tumor response. An increased level of CD19+ subsets was an independent predictor for inferior overall survival. Systemic circulating T cells immunity played an important role and mediating antitumor responses may pave the road for new immunity strategies.

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Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽

10.3390/life11030245 ◽

2021 ◽

Vol 11 (3) ◽

pp. 245

Author(s):

Daniil Shevyrev ◽

Valeriy Tereshchenko ◽

Elena Blinova ◽

Nadezda Knauer ◽

Ekaterina Pashkina ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Autoimmune Diseases ◽

Peripheral Blood ◽

Treg Cells ◽

Homeostatic Proliferation ◽

Suppressive Activity ◽

Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

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Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis

Open Medicine ◽

10.1515/med-2021-0285 ◽

2021 ◽

Vol 16 (1) ◽

pp. 826-832

Author(s):

Jiarong Wang ◽

Liansheng Qiu ◽

Yimin Chen ◽

Minyun Chen

Keyword(s):

T Cells ◽

Allergic Rhinitis ◽

Retrospective Study ◽

Regulatory T Cells ◽

Visual Analog Scale ◽

Peripheral Blood ◽

Sublingual Immunotherapy ◽

Analog Scale ◽

Vas Score ◽

Medication Score

Abstract Background Few studies investigated the effects of sublingual immunotherapy (SLIT) on the peripheral regulatory T cells (Tregs)/Th17 ratio. Objective To investigate the effectiveness of SLIT in children with allergic rhinitis (AR) and the effects on the Tregs/Th17 ratio. Methods This was a retrospective study of children who were treated for AR between April 2017 and March 2018 at one hospital. The patients were grouped according to the treatments they received: SLIT + pharmacotherapy vs pharmacotherapy alone. Results Eighty children (51 boys and 29 girls; 40/group) were included. The visual analog scale (VAS) and medication scores at 1 year in the SLIT + pharmacotherapy group were 2.70 ± 1.08 and 1.1 ± 0.8, respectively, which were lower than at baseline (7.7 ± 1.2 and 3.6 ± 1.0, respectively) (both Ps < 0.05). For the pharmacotherapy group, the VAS score was decreased at 1 year vs baseline (3.3 ± 1.2 vs 7.4 ± 1.0; P < 0.05), but the medication score did not change (P > 0.05). In the SLIT + pharmacotherapy group, the Treg percentage increased, while the Th17 percentage decreased at 1 year (both Ps < 0.01). The percentages of Tregs and Th17s did not change in the pharmacotherapy group (both Ps > 0.05). Conclusions SLIT + pharmacotherapy can increase the Treg percentage and decrease the Th17 percentage in the peripheral blood of children with AR.

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Isolation of functional human regulatory T cells (Treg) from the peripheral blood based on the CD39 expression

Journal of Immunological Methods ◽

10.1016/j.jim.2009.05.004 ◽

2009 ◽

Vol 346 (1-2) ◽

pp. 55-63 ◽

Cited By ~ 106

Author(s):

Magis Mandapathil ◽

Stephan Lang ◽

Elieser Gorelik ◽

Theresa L. Whiteside

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Peripheral Blood

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Expansion of CD4+CD25+FOXP3+ Regulatory T Cells in Peripheral Blood and Skin Lesions of Patients with Atopic Dermatitis

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2007.12.064 ◽

2008 ◽

Vol 121 (2) ◽

pp. S15-S15

Author(s):

Y ITO ◽

T MAKINO ◽

Y ADACHI ◽

H HIGASHIYAMA ◽

T SHIMIZU ◽

...

Keyword(s):

T Cells ◽

Atopic Dermatitis ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Skin Lesions

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Low Frequency of Regulatory T Cells in the Peripheral Blood of Children with Type 1 Diabetes Diagnosed under the Age of Five

Archivum Immunologiae et Therapiae Experimentalis ◽

10.1007/s00005-012-0177-y ◽

2012 ◽

Vol 60 (4) ◽

pp. 307-313 ◽

Cited By ~ 10

Author(s):

Agnieszka Szypowska ◽

Anna Stelmaszczyk-Emmel ◽

Urszula Demkow ◽

Włodzimierz Łuczyński

Keyword(s):

T Cells ◽

Type 1 Diabetes ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Low Frequency

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OR.106. Single-cell Analysis Reveals Non-suppressive CD4+FOXP3+Regulatory T Cells in Human Peripheral Blood

Clinical Immunology ◽

10.1016/j.clim.2009.03.121 ◽

2009 ◽

Vol 131 ◽

pp. S43

Author(s):

Eva d'Hennezel

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Single Cell ◽

Peripheral Blood ◽

Single Cell Analysis ◽

Human Peripheral Blood ◽

Cell Analysis

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Detection of CD4+CD25+FOXP3+ regulatory T cells in peripheral blood of patients with chronic autoimmune urticaria

Australasian Journal of Dermatology ◽

10.1111/j.1440-0960.2010.00658.x ◽

2010 ◽

Vol 52 (3) ◽

pp. e15-e18 ◽

Cited By ~ 8

Author(s):

Ren-Shan Sun ◽

Jian-Feng Sui ◽

Xiao-Hong Chen ◽

Xin-Ze Ran ◽

Zi-Feng Yang ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Autoimmune Urticaria

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Whole-exome sequencing reveals potential germline and somatic mutations in 60 malignant ovarian germ cell tumors

Biology of Reproduction ◽

10.1093/biolre/ioab052 ◽

2021 ◽

Author(s):

Juan Chen ◽

Yan Li ◽

Jianlei Wu ◽

Yakun Liu ◽

Shan Kang

Keyword(s):

Germ Cell ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Peripheral Blood ◽

Copy Number ◽

Somatic Mutations ◽

Germ Cell Tumors ◽

Germline Mutations ◽

Deletion Region ◽

Whole Exome

Abstract Background Malignant ovarian germ cell tumors (MOGCTs) are rare and heterogeneous ovary tumors. We aimed to identify potential germline mutations and somatic mutations in MOGCTs by whole-exome sequencing. Methods The peripheral blood and tumor samples from these patients were used to identify germline mutations and somatic mutations, respectively. For those genes corresponding to copy number alterations (CNA) deletion and duplication region, functional annotation of was performed. Immunohistochemistry was performed to evaluate the expression of mutated genes corresponding to CNA deletion region. Results In peripheral blood, copy number loss and gain were mostly found in yolk sac tumors (YST). Moreover, POU5F1 was the most significant mutated gene with mutation frequency > 10% in both CNA deletion and duplication region. In addition, strong cytoplasm staining of POU5F1 (corresponding to CNA deletion region) was found in 2 YST and nuclear staining in 2 dysgerminomas (DG) tumor samples. Genes corresponding to CNA deletion region were significantly enriched in the signaling pathway of regulating pluripotency of stem cells. In addition, genes corresponding to CNA duplication region were significantly enriched in the signaling pathways of RIG-I-like receptor, Toll-like receptor, NF-kappa B and Jak–STAT. KRT4, RPL14, PCSK6, PABPC3 and SARM1 mutations were detected in both peripheral blood and tumor samples. Conclusions Identification of potential germline mutations and somatic mutations in MOGCTs may provide a new field in understanding the genetic feature of the rare biological tumor type in the ovary.

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