Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory phenotypes without any regulatory/suppressor function

Kmieciak, Maciej; Gowda, Madhu; Graham, Lisa; Godder, Kamar; Bear, Harry D.; Marincola, Francesco M.; Manjili, Masoud H.

doi:10.1186/1479-5876-7-89

Cited by 145 publications

(120 citation statements)

References 27 publications

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“…We used FOXP3 as an initial marker to identify early effectors, because the expression of this transcription factor is upregulated even on CD8 + T-cell activation (19)(20)(21). Expression of FOXP3 has been frequently reported to mark even CD8 + regulatory T lymphocytes found in cancer patients (28)(29)(30)(31)(38)(39)(40) The identification of the CD8 + subset described in this study as "early effectors" was corroborated by several lines of evidence.…”

Section: Discussionmentioning

confidence: 69%

“…In fact, although FOXP3 marks subsets of CD4 + and CD8 + T lymphocytes with regulatory/ suppressive function (see refs. 17, 18, for review), it is also expressed by recently activated T cells that acquire effector functions (19)(20)(21). We found a CD8 + FOXP3 + T-cell subset enriched in TILN compared with TFLN and periphery and in advanced primary lesions compared with TILN.…”

Section: Cd127mentioning

confidence: 60%

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Tumor-Reactive CD8+ Early Effector T Cells Identified at Tumor Site in Primary and Metastatic Melanoma

et al. 2010

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Section: Discussionmentioning

confidence: 69%

Section: Cd127mentioning

confidence: 60%

Tumor-Reactive CD8+ Early Effector T Cells Identified at Tumor Site in Primary and Metastatic Melanoma

et al. 2010

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“…Moreover, we also documented that suppressive T cells in cervical cancer patients had the CD4 + CD25 high Foxp3 + phenotype (23) and that, as in many malignancies, their presence impaired tumor immunity as reflected in worse patient survival (28). In contrast to the antigen-specific stimulation used here, strong mitogenic agents were reported to induce Foxp3 expression in nonsuppressive T cells (29,30). The tumor-specific immune response, the local environment, and immune escape mechanisms in HPV-induced cancers are similar to those in other immunogenic cancer types, and it is likely that the association of treatment failure and vaccine-enhanced Foxp3 + cells we describe can extend to immunotherapy with other tumor antigens.…”

Section: Discussionmentioning

confidence: 90%

Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses

Welters

Kenter

Steenwijk

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

218

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One half of a group of 20 patients with human papillomavirus type 16 (HPV16)-induced vulvar intraepithelial neoplasia grade 3 displayed a complete regression (CR) after therapeutic vaccination with HPV16 E6/E7 synthetic long peptides. Patients with relatively larger lesions generally did not display a CR. To investigate immune correlates of treatment failure, patients were grouped according to median lesion size at study entry, and HPV16-specific immunity was analyzed at different time points by complementary immunological assays. The group of patients with smaller lesions displayed stronger and broader vaccine-prompted HPV16-specific proliferative responses with higher IFNγ (P = 0.0003) and IL-5 (P < 0.0001) levels than patients with large lesions. Characteristically, this response was accompanied by a distinct peak in cytokine levels after the first vaccination. In contrast, the patient group with larger lesions mounted higher frequencies of HPV16-specific CD4 + CD25 + Foxp3 + T cells (P = 0.005) and displayed a lower HPV16-specific IFNγ/IL-10 ratio after vaccination (P < 0.01). No disparity in T memory immunity to control antigens was found, indicating that the differences in HPV-specific immunity did not reflect general immune failure. We observed a strong correlation between a defined set of vaccine-prompted specific immune responses and the clinical efficacy of therapeutic vaccination. Notably, a high ratio of HPV16-specific vaccine-prompted effector T cells to HPV16-specific CD4 + CD25 + Foxp3 + T cells was predictive of clinical success. Foxp3 + T cells have been associated previously with impaired immunity in malignancies. Here we demonstrate that the vaccine-prompted level of this population is associated with early treatment failure.human papilloma virus | immunomonitoring | therapeutic vaccine | regulatory T cells

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“…It is probable that the expression of Foxp3 ocuurs in effector T cells as well as in Tregs. It has been reported that activated T cells can upregulate the expression of Foxp3 (48,49). There are several activated T cells, such as Th1, involved in PBMCs, which may indicate why the expression levels of Foxp3 are upregulated in PBMCs.…”

Section: Discussionmentioning

confidence: 99%

miR‑34a and miR‑125b are upregulated in peripheral blood mononuclear cells from patients with type 2 diabetes mellitus

Yan-xin

Pan

et al. 2017

Exp Ther Med

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Abstract. Type 2 diabetes mellitus (T2DM) is a leading cause of blindness, non-traumatic amputation and end-stage renal disease, as well as a major cardiovascular risk factor. To determine whether miR-125b and miR-34a serve an important role in the development of T2DM, the current study investigated the expression profile of two microRNAs (miR-34a and miR-125b) and their relative genes in peripheral blood mononuclear cells from 73 patients with T2DM and 52 healthy donors by reverse transcription-quantitative polymerase chain reaction In addition, the association between miR-34a, miR-125b and their relevant genes expression profile were analyzed with respect to the pathogenesis of T2DM. The present study demonstrated that the expression levels of miR-125b and miR-34a were elevated in peripheral blood mononuclear cell samples from patients with T2DM. Furthermore, miR-34a and miR-125b were positively correlated with low-density lipoprotein/high-density lipoprotein (HDL) and Foxp3 and negatively related to triglyceride/HDL. However, no correlation among miR-34a, miR-125b and the value of homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function and the genes of B lymphocyte-induced maturation protein-1, interferon regulatory factor-4, P53 and retinoid-related orphan receptor γt were observed. These results indicate that the alteration of miR-34a and miR-125b exists in patients with T2DM, which may be involved in the pathogenesis of T2DM, and could be a potential novel biomarker of T2DM. IntroductionType 2 diabetes mellitus (T2DM), formerly termed non-insulin-dependent diabetes mellitus or adult-onset diabetes, is a multifactor disease that involves complex interactions between genes (1-3), abnormalities of the immune system (4-6), environmental factors (7-10) and health-impacting behavior (11,12), and represents a serious public health problem in numerous developed countries (13). Current investigations have revealed a definite global increase in the incidence and prevalence of diabetes. In 2013, 382 million people worldwide were estimated to be diabetic by the International Diabetes Federation, which is expected to rise to 592 million cases in the year 2035 (14). As a result of the increasing rate of diabetes and its widespread societal and economic consequences, prevention of diabetes among people at high risk is an important public health issue in clinic practice. However, the extent to which multiple defects in the regulation of lipids, insulin secretion and action, and the immune system contribute to the pathogenesis of T2DM has yet to be elucidated.MicroRNAs (miRNAs) are a class of small, single-stranded non-coding RNAs (~22 nucleotides) that are transcribed from the DNA of a gene, and modulate the expression of a network of mRNAs through binding to the 3'-untranslated region (3'-UTR), 5'-UTR or to the open reading frame of target mRNAs (15). Notably, each miRNA is able to target multiple mRNAs. Growing evidence indicates that miRNAs are involved in T2DM (16). However,...

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Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory phenotypes without any regulatory/suppressor function

Cited by 145 publications

References 27 publications

Tumor-Reactive CD8+ Early Effector T Cells Identified at Tumor Site in Primary and Metastatic Melanoma

Tumor-Reactive CD8+ Early Effector T Cells Identified at Tumor Site in Primary and Metastatic Melanoma

Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses

miR‑34a and miR‑125b are upregulated in peripheral blood mononuclear cells from patients with type 2 diabetes mellitus

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