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1.
《Saudi Journal of Biological Sciences》2020,27(10):2645-2650
Stimulation of the neonatal immune system is quite important for the proliferation and differentiation of antigen-presenting cells (APCs) and T cells. Tahneeq is a traditional method to manually rub the palatal mucosa of newborn babies with premasticated Ajwa palm dates. The present study was to investigate the tahneeq effects on IL-12 expression of dendritic cells (DCs) and blood T lymphocytes expressing CD8+ in neonatal Wistar rats. The number of 90 healthy neonatal Wistar rats have randomly divided into three groups: control group received breastmilk only, treatment group (T1) receiving breast milk + mild-scratched intensity of tahneeq, and T2 group received breastmilk + strong-scratched intensity of tahneeq on the palatal and gingival mucosa immediately after birth. Seven neonatal Wistar rats in all groups were then sacrificed in three hours after birth and days 1, 5, 7, 13, and 30 treatment. IL-12 expression in the palatal and gingival mucosa was determined using immunohistochemical staining, and blood CD8+ T-lymphocytes were quantified using a flow cytometer. One way ANOVA was used to analyze the percentage of IL-12 and CD8+ T-lymphocytes among neonatal Wistar rat groups. The T1 and T2 newborn rat groups had significantly higher IL-12 expression than the control group (p<0.001). The increased IL-12 expression in T2 groups significantly increased (p<0.001) compared to the IL-12 expression in the T1 and control groups. The percentage of CD8+ T lymphocytes in all neonatal rat groups increased on three hours after birth and day 30 treatment but remained constant on days 5 and 7 treatment and decreased on day 13 treatment. At 5, 13, and 30th days treatment, the percentage of CD8+ T lymphocytes in T1 and T2 neonatal rat groups was significantly higher (p<0.05) than that in the control group. In conclusion, the impact on systemic CD8+ T cells did not influence by the depth of the scratch. Both mild and strong tahneeq increased the systemic CD8+ T-lymphocytes in neonatal Wistar rats. The roles of anti-inflammatory cytokines and Treg cells should be further investigated to unravel those different results for the development of mucosal immunity in neonates. 相似文献
2.
The CD4+AT2R+ T cell subpopulation improves post‐infarction remodelling and restores cardiac function
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Anna Skorska Stephan von Haehling Marion Ludwig Cornelia A. Lux Ralf Gaebel Gabriela Kleiner Christian Klopsch Jun Dong Caterina Curato Wassim Altarche‐Xifró Svetlana Slavic Thomas Unger Robert David 《Journal of cellular and molecular medicine》2015,19(8):1975-1985
Myocardial infarction (MI) is a major condition causing heart failure (HF). After MI, the renin angiotensin system (RAS) and its signalling octapeptide angiotensin II (Ang II) interferes with cardiac injury/repair via the AT1 and AT2 receptors (AT1R, AT2R). Our study aimed at deciphering the mechanisms underlying the link between RAS and cellular components of the immune response relying on a rodent model of HF as well as HF patients. Flow cytometric analyses showed an increase in the expression of CD4+ AT2R+ cells in the rat heart and spleen post‐infarction, but a reduction in the peripheral blood. The latter was also observed in HF patients. The frequency of rat CD4+ AT2R+ T cells in circulating blood, post‐infarcted heart and spleen represented 3.8 ± 0.4%, 23.2 ± 2.7% and 22.6 ± 2.6% of the CD4+ cells. CD4+ AT2R+ T cells within blood CD4+ T cells were reduced from 2.6 ± 0.2% in healthy controls to 1.7 ± 0.4% in patients. Moreover, we characterized CD4+ AT2R+ T cells which expressed regulatory FoxP3, secreted interleukin‐10 and other inflammatory‐related cytokines. Furthermore, intramyocardial injection of MI‐induced splenic CD4+ AT2R+ T cells into recipient rats with MI led to reduced infarct size and improved cardiac performance. We defined CD4+ AT2R+ cells as a T cell subset improving heart function post‐MI corresponding with reduced infarction size in a rat MI‐model. Our results indicate CD4+ AT2R+ cells as a promising population for regenerative therapy, via myocardial transplantation, pharmacological AT2R activation or a combination thereof. 相似文献
3.
Mitesh Dwivedi Naresh C. Laddha Prateek Arora Yogesh S. Marfatia Rasheedunnisa Begum 《Pigment cell & melanoma research》2013,26(4):586-591
The aim of present study was to evaluate CD4+/CD8+ ratio and CD4+CD25hiFoxP3+ Tregs in GV patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4+/CD8+ ratio and Tregs in 82 patients and 50 controls. CD8+ T‐cell counts were significantly higher in GV patients as compared with controls (p = 0.003). Active GV patients showed higher CD8+ T‐cell counts compared with stable GV patients (p = 0.001). The CD4+/CD8+ ratio decreased significantly in patients as compared with controls (p = 0.001). Moreover, the ratio in active GV patients significantly lowered as compared with stable GV patients (p = 0.002). Significant decrease in Treg cell percentage and counts in GV patients was observed compared with controls (p = 0.009, p = 0.008) with significant reduction in FoxP3 expression (p = 0.024). Treg cell percentage and counts were significantly decreased in active GV patients compared with stable GV patients (p = 0.007, p = 0.002). Our results suggest that an imbalance of CD4+/CD8+ ratio and natural Tregs in frequency and function might be involved in the T‐cell mediated pathogenesis of GV and its progression. 相似文献
4.
5.
《Journal of cellular and molecular medicine》2017,21(5):975-985
This study aims to explore effects of 1,25(OH)2D3 and vitamin D receptor (VDR) on peripheral CD4+/CD8+ double‐positive (DP) T lymphocytes in systemic lupus erythematosus (SLE). MRL‐LPr/LPr mice with SLE (n = 20) and normal MRL mice (n = 20) were assigned into the control group (normal mice, without feeding with 1,25(OH)2D3), the 1,25(OH)2D3 group (SLE mice, feeding with 1,25(OH)2D3), the VDR‐knock‐in + 1,25(OH)2D3 group (SLE mice, VDR‐knock‐in, feeding with 1,25(OH)2D3) and the VDR‐knockout group (normal mice, VDR‐knockout, without feeding with 1,25(OH)2D3) (n = 10 per group). Levels of T lymphocytes were measured by flow cytometry. The mRNA and proteins expressions of inflammatory factors were measured by qRT‐PCR and ELISA. Extracellular signal‐regulated kinase‐1/2 (ERK1/2) expression was measured by Western blotting. Compared with normal mice, SLE mice showed reduced levels of CD4+, CD4+/CD8+ ratio, and DP lymphocytes. The levels of SLE‐related indicators all increased significantly, followed with severe skin ulcers and urinary system infection. With the increase in time, skin ulcers and urinary system infection were significantly improved, levels of CD4+, CD4+/CD8+ ratio, and DP lymphocytes increased, and levels of SLE‐related indicators all decreased in the 1,25(OH)2D3 group. There were no significant changes in bioindicators in the control and the VDR‐knock‐in + 1,25(OH)2D3 groups. The symptoms of SLE gradually occurred in the VDR‐knockout group. This study demonstrates that VDR and 1,25(OH)2D3 could elevate CD4+/CD8+ DP T lymphocytes and reduce expressions of inflammatory factors, thus inhibiting the development and progression of SLE. 相似文献
6.
Jianguo Wu Hongyan Cui Zhifeng Zhu Li Wang Hong Li Desheng Wang 《Microbiology and immunology》2014,58(7):409-415
7.
CD58/LFA-3 and IL-12 provided by activated monocytes are critical in the in vitro expansion of CD56+ T cells 总被引:9,自引:0,他引:9
A small proportion of human CD3+ T lymphocytes are known to co-express CD56, an antigen usually restricted in its expression to natural killer (NK) cells.
Whereas the in vivo function of CD3+ CD56+ T cells remains unknown, we and others have previously shown that both in vitro and in vivo, these cells can mediate a significantly
greater degree of MHC-unrestricted cytotoxicity against a variety of human tumor cells when compared to either CD3+ CD56− T cells or lymphokine activated killer (LAK) cells. While the mechanisms regulating the in vivo expansion of CD56+ T cells are not known, here we demonstrate the importance of CD2-mediated IL-12-dependent signals in the in vitro expansion
of CD56+ T cells. Specifically, we show that activated monocytes provide a contact dependent factor (CD58/LFA-3) and a soluble factor
(IL-12), both critical for the in vitro expansion of CD56+ T cells. The biological and therapeutic implications of these findings are discussed.
Received: 4 May 2000 / Accepted: 25 August 2000 相似文献
8.
Harrop R Ryan MG Myers KA Redchenko I Kingsman SM Carroll MW 《Cancer immunology, immunotherapy : CII》2006,55(9):1081-1090
5T4 is a tumor associated antigen that is expressed on the surface of a wide spectrum of human adenocarcinomas. The highly attenuated virus, modified vaccinia Ankara, has been engineered to express human 5T4 (h5T4). In a pre-clinical murine model, the recombinant virus (TroVax) induces protection against challenge with CT26–h5T4 (a syngeneic tumor line expressing h5T4). Anti-tumor activity is long lived, with protection still evident 6 months after the final vaccination. In a therapeutic setting, injection of mice with TroVax results in a reduction in tumor burden of >90%. Depletion of CD8+ T cells has no effect upon therapy in the active treatment model, whereas depletion of CD4+ T cells completely abrogates anti-tumor activity. In a prophylactic setting, depletion of CD4+ and CD8+ T cells after the induction of a h5T4 immune response has no deleterious effect on protection following challenge with CT26–h5T4. In light of these studies, the role of antibodies in protection against tumor challenge was investigated. 5T4 specific polyclonal serum decreased tumor burden by approximately 70%. Thus, we conclude that CD4+ T cells are essential for the induction of a protective immune response and that antibodies are the likely effector moiety in this xenogeneic murine tumor model. 相似文献
9.
Olivia Briceño Anna Lissina Kerstin Wanke Georgia Afonso Amrei von Braun Kristanto Ragon Tiphaine Miquel Emma Gostick Laura Papagno Karin Stiasny David A. Price Roberto Mallone Delphine Sauce Urs Karrer Victor Appay 《Aging cell》2016,15(1):14-21
Aging is associated with impaired vaccine efficacy and increased susceptibility to infectious and malignant diseases. CD8+ T‐cells are key players in the immune response against pathogens and tumors. In aged mice, the dwindling naïve CD8+ T‐cell compartment is thought to compromise the induction of de novo immune responses, but no experimental evidence is yet available in humans. Here, we used an original in vitro assay based on an accelerated dendritic cell coculture system in unfractioned peripheral blood mononuclear cells to examine CD8+ T‐cell priming efficacy in human volunteers. Using this approach, we report that old individuals consistently mount quantitatively and qualitatively impaired de novo CD8+ T‐cell responses specific for a model antigen. Reduced CD8+ T‐cell priming capacity in vitro was further associated with poor primary immune responsiveness in vivo. This immune deficit likely arises as a consequence of intrinsic cellular defects and a reduction in the size of the naïve CD8+ T‐cell pool. Collectively, these findings provide new insights into the cellular immune insufficiencies that accompany human aging. 相似文献
10.
Tomohiko Ishimine Kazuyoshi Kawakami Atsushi Nakamoto Atsushi Saito 《Microbiology and immunology》1995,39(1):49-58
The cellular and cytokine responses in the lungs of mice infected with Pneumocystis carinii were examined on both lung homogenates and bronchoalveolar lavage (BAL) fluids. In the lungs of infected mice, the number of P. carinii cysts rapidly decreased by day 7, then started to increase with a peak on day 14, and thereafter decreased gradually. When the presence of P. carinii was examined at the DNA level by dot blot hybridization, a similar clearance curve was obtained, and the organisms were shown to be completely eliminated on day 28. In the late phase of infection, leukocytes, mainly lymphocytes, increased in number when analyzed on lung homogenates, while no significant increase of inflammatory cells was observed in BAL fluids. An accumulation of both CD4+ and CD8+ T cells and an increase of activated T cells expressing IL-2Rα were observed in lung homogenates of the infected mice. In addition, a considerable amount of IFN-γ was detected in lung homogenates, but not in BAL fluids. These data indicate that lung homogenates are more suitable than BAL fluids for the analysis of cellular and cytokine responses in the lungs of mice infected with P. carinii. To define the involvement of IFN-γ in host defense against P. carinii, the effect of this cytokine on the killing activity of macrophages against P. carinii was examined in vitro. IFN-γ was found to augment this activity by increasing nitric oxide synthesis of the macrophages. Thus, it is suggested that IFN-γ plays an important role in the protection of mice from P. carinii infection. 相似文献
11.
Fumiyoshi Okano Hirofumi Tachibana Koichi Akiyama Sanetaka Shirahata Hiroki Murakami 《Cytotechnology》1993,11(3):205-211
Immortalized human T cell lines were established by cotransfecting c-Ha-ras and c-myc oncogenes to lymph node lymphocytes. The cell lines kept growing for 3 months after establishment without a decrease in growth rate. The cells did not require interleukin-2(IL-2) for their growth, but addition of IL-2 stimulated the growth of these cells. Flow cytometric analysis revealed that these cells were T cells expressing CD4 or CD8 antigens. A CD4 positive (CD4+) cell line produced IL-6, indicating that the cell line belongs to helper T cells. The CD8 positive (CD8+) cell line possessed cytotoxicity to tumor cells, indicating that the cell line were killer T cells. Both cell lines were able to proliferate in serum-free medium indefinitely. 相似文献
12.
Phenotypic characteristics of aged CD4+ CD28null T lymphocytes are determined by changes in the whole‐genome DNA methylation pattern
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Beatriz Suarez‐Álvarez Ramón M. Rodríguez Karin Schlangen Aroa Baragaño Raneros Leonardo Márquez‐Kisinousky Agustín F. Fernández Carmen Díaz‐Corte Ana M. Aransay Carlos López‐Larrea 《Aging cell》2017,16(2):293-303
Aging is associated with a progressive loss of the CD28 costimulatory molecule in CD4+ lymphocytes (CD28null T cells), which is accompanied by the acquisition of new biological and functional properties that give rise to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset during aging and in several associated inflammatory disorders remain controversial. Here, we present the whole‐genome DNA methylation and gene expression profiles of CD28null T cells and its CD28+ counterpart. A comparative analysis revealed that 296 genes are differentially methylated between the two cell subsets. A total of 160 genes associated with cytotoxicity (e.g. GRZB, TYROBP, and RUNX3) and cytokine/chemokine signaling (e.g. CX3CR1, CD27, and IL‐1R) are demethylated in CD28null T cells, while 136 de novo‐methylated genes matched defects in the TCR signaling pathway (e.g. ITK, TXK, CD3G, and LCK). TCR‐landscape analysis confirmed that CD28null T cells have an oligo/monoclonal expansion over the polyclonal background of CD28+ T cells, but feature a Vβ family repertoire specific to each individual. We reported that CD28null T cells show a preactivation state characterized by a higher level of expression of inflammasome‐related genes that leads to the release of IL‐1β when activated. Overall, our results demonstrate that CD28null T cells have a unique DNA methylation landscape, which is associated with differences in gene expression, contributing to the functionality of these cells. Understanding these epigenetic regulatory mechanisms could suggest novel therapeutic strategies to prevent the accumulation and activation of these cells during aging. 相似文献
13.
Elkord E Burt DJ Drijfhout JW Hawkins RE Stern PL 《Cancer immunology, immunotherapy : CII》2008,57(6):833-847
Background The human 5T4 (h5T4) oncofoetal antigen is expressed by a wide variety of human carcinomas including colorectal, ovarian,
gastric and renal, but rarely on normal tissues. Its restricted expression on tumour tissues as well as its association with
tumour progression and bad prognosis has driven the development of a MVA-based vaccine (TroVax) which has been tested in several
early phase clinical trials and these studies have led to the start of a phase III trial in renal cell carcinoma patients.
We have recently shown that CD8+ T cells recognizing h5T4 can be generated in the absence of CD4+ T cells from peripheral blood lymphocytes of human healthy individuals.
Results We report the existence and expansion of human CD4+ T cells against h5T4 by stimulation with autologous monocyte-derived dendritic cells infected with a replication defective
adenovirus encoding the h5T4 cDNA (Ad-h5T4). The h5T4-specific T-cell responses in normal individuals are enhanced by initial
depletion of CD25+ cells (putative T regulatory cells) prior to the in vitro stimulation. We have identified a novel h5T4-derived 15-mer peptide
recognized by CD4+ T cells in HLA-DR4 positive healthy individuals. Interestingly, CD4+ T cells spontaneously recognizing a different 5T4 epitope restricted by HLA-DR were identified in tumour-infiltrating lymphocytes
isolated from a regressing renal cell carcinoma lung metastasis.
Conclusion Our data show that CD4+ T cells recognizing h5T4 can be expanded and detected in healthy individuals and a renal cell carcinoma patient. Such h5T4-specific
CD4+ T cells boosted or induced by vaccination could act to modulate both cell or antibody mediated anti-tumour responses.
This work was supported by Cancer Research UK. 相似文献
14.
Expression of PD‐1/LAG‐3 and cytokine production by CD4+ T cells during infection with Plasmodium parasites
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Henrietta T. Doe Daisuke Kimura Mana Miyakoda Kazumi Kimura Masoud Akbari Katsuyuki Yui 《Microbiology and immunology》2016,60(2):121-131
15.
Yumiko Nagai Manabu Inobe Kokichi Kikuchi Toshimitsu Uede 《Microbiology and immunology》1993,37(8):623-632
Rat CD4+ T cells were divided into two distinct subsets by a monoclonal antibody RTH-1 recognizing a unique epitope on rat CD45R. Cellular distribution of OX-22- and RTH-1-defined antigens was the same. However, OX-22 and RTH-1 recognized different epitopes that exist on rat CD45R. The expression of IL-4 gene was detected only in RTH-1low CD4+ T cell subset upon various stimulations. In contrast, the expression of IL-2 and IFN-γ gene varied depending upon the nature of stimuli. The increased cell surface expression of CD44 was detected in RTH-1high CD4+ T cell subset. Conversely the increased expression of CD2 was detected in RTH-1low CD4+ T cell subset. The expression of CD3 and LFA-1 was not significantly different between RTH-1high and RTH-1low subsets. 相似文献
16.
In this study, we have characterised postnatal changes in T lymphocyte subsets, especially γδ T lymphocytes, in blood, spleen and lymph nodes. Detection was carried out using two-colour flow cytometry and three-colour immunohistochemistry. During ontogeny, there was a significant increase in the total percentage of γδ T cells in the spleen and blood. In the lymph nodes, there were no age-dependent changes in the total percentage of γδ T cells, but the percentage of the γδTCR+CD8+ subpopulation significantly increased. The tissue distribution of γδTCR+CD8+ and γδTCR+CD8− cells in the lymph nodes is random and not collocated with a particular area of the organ. Furthermore, postnatal development was characterised by an increasing frequency of CD8+CD3+CD4−γδTCR−, which was compensated by a decreasing proportion of CD4+ lymphocytes. Double positive CD4+CD8+ lymphocytes were rare during the first month of life and a significant age-dependent increase of these cells was found in all the compartments monitored. 相似文献
17.
摘要 目的:研究肺癌患者外周血T淋巴细胞分型与抗核抗体之间的关系。方法:选择2019年1月到2021年6月在我院接受治疗的肺癌患者81例作为研究组,并选择同期健康志愿者81例作为对照组,检测并比较两组患者外周血CD4+、CD8+和CD4+/CD8+淋巴细胞比例,以及抗核抗体血清滴度。比较不同抗核抗体、年龄、性别、TNM分期、肿瘤分化程度以及病理类型肺癌患者外周血CD4+、CD8+和CD4+/CD8+淋巴细胞比例。结果:(1)肺癌患者外周血CD4+和CD4+/CD8+淋巴细胞比例显著低于对照组,而CD8+淋巴细胞比例显著高于对照组(P<0.05);(2)III+IV肺癌患者外周血CD4+、和CD4+/CD8+淋巴细胞比例均显著低于I+II肺癌患者,而CD8+淋巴细胞比例均显著高于I+II肺癌患者(P<0.05);(3)小细胞肺癌患者外周血CD4+、和CD4+/CD8+淋巴细胞比例均显著低于非小肺癌患者,而CD8+淋巴细胞比例均显著高于非小肺癌患者(P<0.05);(4)肺癌患者抗核抗体血清滴度显著高于对照组(P<0.05);(5)抗核抗体阳性患者CD4+和CD4+/CD8+淋巴细胞亚群比例均显著低于抗核抗体阴性患者,而CD8+淋巴细胞亚群比例显著高于抗核抗体阴性患者(P<0.05)。结论:肺癌患者外周血T淋巴细胞亚群表达异常,并且其表达水平可能与抗核抗体滴度有关。 相似文献
18.
19.
Role of T‐bet,the master regulator of Th1 cells,in the cytotoxicity of murine CD4+ T cells
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Koji Eshima Kana Misawa Chihiro Ohashi Kazuya Iwabuchi 《Microbiology and immunology》2018,62(5):348-356
20.
Jian-Guo Chai Tohru Sakai Hajime Hisaeda Hideyuki Nagasawa Koji Yasutomo Atuko Furukawa Hiroyuki Ishikawa Yoichi Maekawa Hisanori Uehara Keisuke Izumi Kozo Matsumoto Kunisuke Himeno 《Microbiology and immunology》1996,40(9):659-664
We reported that LEC rats are genetically deficient in the development of thymic CD4+8? cells and that this defect is caused by bone marrow (BM)-derived stem cells. To determine which BM-derived cells are responsible for the arrest of T-cell development in LEC rats, fetal thymuses of LEC rats, or LEA rats which bear the same major histocompatibility complex (MHC) as LEC rats but are immunologically normal, were engrafted under the kidney capsule of severe combined immunodeficiency (SCID) mice (LEC-TG and LEA-TG mice, respectively). We then examined the differentiation of T cells and their immunological functions in the SCID mice. A large number of rat-derived CD4+ T cells appeared in the peripheral blood, lymph nodes (LN) and spleens in LEC-TG mice. Furthermore, the peripheral LN cells in LEC-TG mice appeared to be functional. These cells produced IL-2 upon Con A stimulation, whereas LN cells from LEC rats produced no IL-2 in the same conditions. Thymopoiesis was observed at 3 weeks in LEC-TG as well as LEA-TG mice. The distribution of thymocyte subsets with respect to CD4 and CD8 expression in LEC-TG mice closely resembled that of LEA rat thymus and that in LEA-TG mice, suggesting that normal T-cell differentiation occurred in LEC-TG mice. The results indicated that BM-derived progenitor T cells of LEC rats could differentiate to functional CD4+ T cells. 相似文献