|Year : 2012 | Volume
| Issue : 6 | Page : 952-957
Regulatory T cells in children with recently diagnosed type 1 diabetes
Asmaa Mohamed Zahran1, Khalid Ibrahem Elsayh2, Kotb Abbass Metwalley2
1 Department of Clinical Pathology, South Egypt Cancer Institute, Egypt
2 Department of Pediatric, Faculty of Medicine, Assiut University, Egypt
|Date of Web Publication||31-Oct-2012|
Kotb Abbass Metwalley
Department of Pediatric, Faculty of Medicine, Assiut University
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Regulatory T cells have an important role in the control of immune reactivity against self antigens and probably play a role in pathogenesis of type 1 diabetes (T1D). We aimed to determine the frequency of regulatory T cells in recently diagnosed children with/T1D. Materials and Methods: 20 children with/T1D and 20 healthy children of matched age and sex as controls were enrolled in this study. All cases were subjected to a thorough history taking, full clinical examinations and investigations which include; insulin C peptide levels and flow cytometric detection of B-, T-lymphocytes and regulatory T cells. Results: Insulin C peptide level was significantly lower in children with/ T1D compared with controls. The percentages of B and T-lymphocytes were not significantly different between patients and controls. The percentages of CD4+CD25+High and CD4+CD25+High Foxp3+ cells both in total lymphocytes and in CD4+ lymphocytes were significantly decreased in patients than controls, while the percentages of total CD4+CD25+ and CD4+CD25+Intermediate both in total lymphocytes and in CD4+ lymphocytes were not significantly different between patients and controls. The geometric mean of fluorescence intensity (MFI) of Foxp3+ expression in CD4+CD25+High cells was significantly decreased in patients than controls. Positive correlations were observed between both age and insulin C peptide and frequency of CD4+CD25+High Foxp3. Conclusion: The percentage of regulatory T cells; CD4+CD25+High Foxp3 was decreased in children with recent T1D and may have a role in its pathogenesis. Their role as a prognostic signifi cance and their relation to various complications should be explored.
Keywords: Insulin C peptide, regulatory T cell, type 1 diabetes
|How to cite this article:|
Zahran AM, Elsayh KI, Metwalley KA. Regulatory T cells in children with recently diagnosed type 1 diabetes. Indian J Endocr Metab 2012;16:952-7
|How to cite this URL:|
Zahran AM, Elsayh KI, Metwalley KA. Regulatory T cells in children with recently diagnosed type 1 diabetes. Indian J Endocr Metab [serial online] 2012 [cited 2019 Nov 15];16:952-7. Available from: http://www.ijem.in/text.asp?2012/16/6/952/102998
| Introduction|| |
Type 1 diabetes (T1D), is a chronic autoimmune disease and it is common in children The body's own immune system attacks the beta-cells in the islets of Langerhans of the pancreas, destroying or damaging them. It can lead to long-term complications including cardiovascular disease, blindness and kidney failure.  The damage of the beta-cells in the islets of Langerhans which caused by cytotoxic lymphocytes results in insulin deficiency and hyperglycemia. Environmental factors trigger/T1D in genetically susceptible individuals.  Autoreactive T-cells that recognize islet autoantigens have been identified and are thought to play a direct role in T1D immunopathogenesis.  The breakdown of beta cell-specific self-tolerance by T lymphocytes involves a number of dysregulated events intrinsic and extrinsic to T cells. The peripheral tolerance to self antigens is maintained through several regulatory mechanisms, including T regulatory cells. T regulatory cells are minor population of CD4+ T cells express high levels of CD25. It has an important role in the control of immune reactivity against self antigens, and probably plays a role in pathogenesis of T1D. , Different studies ,,,, had recently reported findings related to the frequency and function of regulatory T cells in T1D, but their results represents a somewhat conflicting body of findings. We aimed to estimate the frequency of regulatory T cells in recently diagnosed diabetes in children attending Assiut Children University Hospital, Egypt.
| Patients and Methods|| |
Patients populations and sampling protocol
All aspects of this study were approved by the Assiut University Institutional Review Board. Patients and controls were enrolled after obtaining the informed consent from the parents. Twenty patients meeting the diagnostic criteria of T1D  were recruited consecutively at the Pediatric Clinical Endocrinology Unit, Children Hospital of Assiut University, Faculty of Medicine. In addition to twenty children with age and sex-matched, none of whom had either a personal or family history of diabetes or other autoimmune pathologies as control were included in the study.
- Definite diagnosis of T1D according to the definition of the World Health Organization criteria  that defines this form of diabetes with permanent insulinopenia prone to ketoacidosis, result from a cellular-mediated autoimmune destruction of the beta cells of the pancreas.
- On insulin replacement therapy.
- Age range 2-16 years.
- Diabetic duration less than 12 weeks.
- Children with secondary diabetes mellitus (DM).
- Children with type 2 DM.
- Evidence of active infection requiring antibiotic therapy or other concurrent diseases.
- Other autoimmune disease.
- Age < 2 years >16 years.
| Methodology|| |
All cases were subjected to:
- Full history including demographic factors: age, sex, residence, family history of diabetes.
- Full clinical examination.
- Complete blood count (Celltac E automated hematology analyzer, Tokyo, Japan).
- Serum insulin C-peptide levels were measured by radioimmunoassay using commercial kits (Diagnostic Systems Laboratories Inc, Webster, Texas). Fasting normal insulin C peptide=0.78-5.19 ng/ml. 
- Flow cytometric detection of regulatory T cells, B-lymphocytes and T-lymphocytes.
Flow cytometric detection of regulatory T cells, B-lymphocytes and T-lymphocytes
CD4 + CD25 + Foxp3 + regulatory T cells in whole blood samples were enumerated using fluoroisothiocyanate (FITC)-conjugated forkhead box protein 3 (Foxp3) (e Bioscience, USA), phycoerythrin (PE) conjugated CD25 (IQ Product, The Netherland) and peridinium-chlorophyll-protein (Per-CP)-conjugated CD4 (Becton Dickinson, Bioscience, USA). Fifty μl of blood sample was incubated with 10 μl of CD4, CD25 for 15 minutes at room temperature in the dark. Following incubation, RBC lysis, washing with phosphate buffer saline (PBS), addition of fixed solution to fix the cells and incubation for 10 minutes were done. After incubation, cells were washed with PBS, and then permelized solution and 10 μl of Foxp3 were added and incubated for 30 minutes at room temperature. For detection of B- and T-lymphocytes, 50 μl of blood sample was stained with 10 μl of FITC-conjugated CD19 and PE-conjugated CD3 (Becton Dickinson Biosciences, USA). The tubes were incubated for 15 minutes at room temperature in the dark. RBC lysis was done. After one wash, the cells were resuspended in PBS. Flow cytometric analysis was done by FACSCalibur flow cytometry with CellQuest software (Becton Dickinson Biosciences, USA). An isotype-matched negative control was used with each sample. Forward and side scatter histogram was used to define the lymphocyte population (R1). Total CD4 + CD25 + , CD4 + CD25 +intermediate , CD4 + CD25 +High (defined as the population of CD4 positive T cells whose CD25 expression exceeded the level of CD25 positivity seen in the CD4 negative T cells) [12,13] and CD4 + CD25 +High Foxp3 + regulatory T cells was evaluated as a percentage of total lymphocytes and of CD4 + as shown in [Figure 1]. The expression of Foxp3 + in CD4 + CD25 +intermediate and in CD4 + CD25 +high cells was expressed as geometric mean of fluorescence intensity (MFI).
|Figure 1: Flow cytometric detection of regulatory T cells. (a) Forward and side scatter histogram was used to define the lymphocytes population (R1). (b,c) The expression of CD4 and CD25 in total lymphocytes (R1) was detected, compared with the negative isotype control and and different gates were drown to define CD4+ CD25-cells (R2), CD4+CD25+intermediate (med) cells (R3), and CD4+CD25+High cells (R4). (d) The percentage of CD4+CD25+high FoxP3+cells (R5) in total lymphocytes was determined. (e-g) Show the analysis of regulatory T cells in CD4+ cells (R 6). CD4+ CD25-cells (R7), CD4+CD25+intermediate (med) cells (R8), and CD4+CD25+High cells (R9). (h) Show the expression as a geometric mean of fluorescence intensity (MFI) of FoxP3+ in CD4+CD25+high cells. The positivity was defined as fluorescence (red histogram) higher than that of the isotype control (open histogram)|
Click here to view
Statistical package for social sciences (SPSS), version 16 was used for data analysis. All data were expressed as the mean± standard error of mean (SEM). Due to the small sample size and a propensity for outliers in some of the variables, Mann-Whitney analysis was used to detect the statistical significance differences between groups. A P value of ≤0.05 denoted the presence of a statistically significant difference.
| Results|| |
Some demographic and clinical data of diabetic children and controls were presented in [Table 1].
|Table 1: Some demographic and clinical data of diabetic children and control|
Click here to view
There were no significant difference in white blood cells count, platelet count and hemoglobin concentration between diabetic patients and controls [Table 2]. The level of insulin C peptide was significantly lower in children with/T1D compared with controls with P < 0.000.
|Table 2: Some laboratory characteristics of diabetic patients and controls|
Click here to view
There were no significant difference in the percentages of T lymphocytes (CD3 + ), B lymphocytes (CD19 + ) and T helper cells (CD4 + ) between patients than controls [Table 3]. The percentages of total CD4 + CD25 + and CD4 + CD25 +Intermediate in total lymphocytes were not significantly different between patients and controls. The percentages of CD4 + CD25 +High and CD4 + CD25 +High Foxp3 + in total lymphocytes were significantly decreased in patients than controls. Similar results were observed when these cells were analyzed as a percentage of CD4 + T cells.
The MFI of Foxp3 + expression in CD4 + CD25 +High Foxp3 cells was significantly decreased in patients than controls, while MFI of Foxp3 + expression in CD4 + CD25 +Intermediate cells was not significantly different between patients and controls [Table 3].
The frequency of CD4 + CD25 +High Foxp3 was positively correlated with age of the patients (r = 0.585, P < 0.000), and the level of insulin C peptide (r = 682, P < 0.000) [Figure 2] and [Figure 3].
|Figure 2: Correlations between the frequency of CD4+CD25+HighFoxp3 and age of diabetic patients|
Click here to view
|Figure 3: Correlations between the frequency of CD4+CD25+HighFoxp3 and level of insulin C peptide|
Click here to view
| Discussion|| |
Type 1 diabetes is a well-known autoimmune disease; however there are still some processes in its pathogenesis to be elucidated. T regulatory cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. These cells modulate the intensity and quality of immune reactions through attenuation of the cytolytic activities of reactive immune cells. 
In this study, CD4 + CD25 +High Foxp3 + cells were considered as regulatory T cells, as the suppressive capacity of regulatory T cells in humans seems to be confined to CD4 + CD25 + cells with the highest expression of CD25 (CD4 + CD25 High , whereas CD4 + T cell with intermediate expression of CD25 might also contain recently activated T cells and effector T-cells without regulatory function. ,, Also, the identification of Foxp3 as a regulatory lineage specific factor provided a useful phenotypic and optimal marker for regulatory T cells, ,, and the suppressive phenotype and the development of regulatory function depend on the expression of Foxp3. ,,, Indeed, recent results indicate that Foxp3 behaves as a master regulator of the regulatory T cells phenotype.
We found the frequency of CD4 + CD25 +High and CD4 + CD25 +High Foxp3 + both in total lymphocytes and in CD4 + cells were significantly decreased in diabetic patients than controls while the frequency of total CD4 + CD25 + and CD4 + CD25 +Intermediate both in total lymphocytes and in CD4 + cells were not significantly different in patients and controls. This decline in the frequency of CD4 + CD25 +High and CD4 + CD25 +High Foxp3 + T cells in our patients could implies that the deficiency of regulatory T cells may has a role in the pathogenesis of type 1 diabetes. In accordance with our results, Luczyñski et al.,  found a statistically significant decrease of T regulatory cells in children with newly diagnosed/T1D. Ryba et al.,  also reported lower percentage of regulatory T cells in children with/T1D. Luczyρski et al.,  reported that percentage of CD4 + CD25 +High was decreased in diabetic patients than controls, the same as our study, while the percentages of CD4+CD25highCD127dim/- were very low and did not differ between T1D and control children and this difference could be due to the of different markers of regulatory T cells they used, CD127dim/- and not foxp3 as our study.
Brusko et al. Putnam et al. and Lindley et al.,  reported that there is no difference in the level of regulatory T cells between patients with/T1D and healthy controls. However, in these studies, the patients were adult  or have long lasting diabetes.  In Brusko et al.,  their patients and controls are older than our patients, and their controls from considerably older than their patients.
Glisic-Milosavljevic et al.,  reported that there is a higher level of ongoing apoptosis in CD4+CD25+ High T cells in recent-onset T1D subjects and in subjects at high risk for the disease. On the contrary, in long-standing/T1D and/T2D subjects, CD4+CD25+ high T cell apoptosis is at the same level as in control subjects. This high level of CD4+CD25+ High T-cell apoptosis could explain the decrease of regulatory T cells in our patients.
Foxp3, is a critical molecular switch for the genetic programming of natural regulatory T cell development and function. , In this study; the MFI of foxp3 expression in CD4 + CD25 High cells were 44.68 ± 2.34 and 74.81 ± 3.47 in patients and controls respectively, while the MFI of foxP3 expression in CD4 + CD25 intermediate were 29.05 ± 2.49 and 37.09 ± 3.50 in patients and controls respectively. These results are consistent with those of Qian et al.
The expression of Foxp3 + in CD4 + CD25 +High Foxp3 cells was significantly decreased in diabetic patients than controls, while its expression in CD4 + CD25 +Intermediate cells was not significantly different between patients and controls. Lawson et al. reported that there was no difference in Foxp3 expression on CD4 + CD25 High T cells in patients with/T1D, but in contrast to our study the patients had long standing diabetes, and both patients and controls were adult subjects. 
In the present study, CD4 + CD25 +High Foxp3 was positively correlated with age of diabetic children. Brusko et al.,  reported in their study that increasing age was associated with an increase in total CD4 + CD25 + frequency.
In the present study, Insulin C peptide level was significantly lower in children with/T1D compared with control. In addition, the frequency of CD4 + CD25 +High Foxp3 was positively and significanty correlated with the level of insulin C peptide. Insulin C-peptide level is the most reliable factor in evaluation of the endogenous insulin secretion in patients with/T1D. Autoimmune destruction of the beta cells of pancreas results in deficiency of both insulin and insulin C-peptide. 
| Conclusions|| |
This study concluded that children with/T1D have lower percentages of T regulatory cells in the peripheral blood which correlated positively with age of patients and the level of insulin C peptide.
Limitations of the study
- The percentages of regulatory T cells were assessed in the peripheral blood but not at the site of affection (pancreas and/or draining lymph nodes).
- The distinction of regulatory T cells by a flow cytometry including-high expression of CD25 antigen is very subjective and can result in different findings from different laboratories.
| References|| |
|1.||£uczynski W, Wawrusiewicz-Kurylonek N, Stasiak-Barmuta A, Urban R, I³endo E, Urban M, et al . Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes. Acta Biochim Pol 2009;56:361-70. |
|2.||van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: Etiology, immunology, and therapeutic strategies. Physiol Rev 2011;91:79-118. |
|3.||Roep BO. The role of T-cells in the pathogenesis of Type 1 diabetes: From cause to cure. Diabetologia 2003;46:305-21. |
|4.||Bluestone JA, Tang Q, Sedwick CE. T regulatory cells in autoimmune diabetes: Past challenges, future prospects. J Clin Immunol 2008;28:677-84. |
|5.||Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 2004;199:971-9. |
|6.||Luczynski W, Stasiak-Barmuta A, Urban R, Urban M, Florys B, Hryszko M. Lower percentages of T regulatory cells in children with type 1 diabetes - preliminary report. Pediatr Endocrinol Diabetes Metab 2009;15:34-8. |
|7.||Ryba M, Hak L, Zorena K, Mysliwiec M, Mysliwska J. [Regulatory T lymphocytes expressing L-selectin in children and adolescents with type 1 diabetes mellitus]. Pediatr Endocrinol Diabetes Metab 2010;16:12-6. |
|8.||Luczynski W, Stasiak-Barmuta A, Mysliwiec M, Niko³ajuk A, Brandt A, Urban R, et al . [Higher percentages of T regulatory cells in children at risk for developing type 1 diabetes mellitus]. Pediatr Endocrinol Diabetes Metab 2010;16:7-10. |
|9.||Brusko T, Wasserfall C, McGrail K, Schatz R, Viener HL, Schatz D, et al. No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetes. Diabetes 2007;56:604-12. |
|10.||American Diabetes Association (ADA). Diagnosis and classification of diabetes mellitus. Diabetes Care 2010:33:S62-9. |
|11.||Raz I, Elias D, Avron A, Tamir M, Metzger M, Cohen IR. Beta-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): A randomised, double- blind, phase II trial. Lancet 2001;358:1749-53. |
|12.||Zhu LY, Chi LJ, Wang X, Zhou H. Reduced circulating CD4+CD25+ cell populations in haemorrhagic fever with renal syndrome. Clin Exp Immunol 2009;156:88-96. |
|13.||Chi LJ, Lu HT, Li GL, Wang XM, Su Y, Xu WH,et al Involvement of T helper type 17 and regulatory T cell activity in tumour immunology of bladder carcinoma. Clin Exp Immunol 2010;161:480-9. |
|14.||Antons AK, Wang R, Oswald-Richter K, Tseng M, Arendt CW, Kalams SA, et al. Naive precursors of human regulatory T cells require FoxP3 for suppression and are susceptible to HIV infection. J Immunol 2008;180:764-73. |
|15.||Moon HW, Kim BH, Park CM, Hur M, Yun YM, Kim SY, et al. CD4 + CD25 high FoxP3 + regulatory T-cells in hematologic diseases. Korean J Lab Med 2011;31:231-7. |
|16.||Stasi R, Cooper N, Del Poeta G, Stipa E, Laura Evangelista M, Abruzzese E, et al. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood 2008;112:1147-50. |
|17.||Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol 2008;8:523-32. |
|18.||Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008;133:775-87. |
|19.||Alatrakchi N, Koziel M. Regulatory T cells and viral liver disease. J Viral Hepat 2009;16:223-9. |
|20.||Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005;22:329-41. |
|21.||Sakaguchi S. Naturally arising CD4 + regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004;22:531-62. |
|22.||Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4 + CD25 + T regulatory cells. Nat Immunol 2003;4:337-42. |
|23.||Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003;299:1057-61. |
|24.||Fontenot JD, Rudensky AY. A well adapted regulatory contrivance: Regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 2005;6:331-7. |
|25.||Putnam AL, Vendrame F, Dotta F, Gottlieb PA. CD4+CD25high regulatory T cells in human autoimmune diabetes. J Autoimmun 2005;24:55-62. |
|26.||Lindley S, Dayan CM, Bishop A, Roep BO, Peakman M, Tree TI. Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 2005;54:92-9. |
|27.||Glisic-Milosavljevic S, Waukau J, Jailwala P, Jana S, Khoo HJ, Albertz H, et al. At-risk and recent-onset type 1 diabetic subjects have increased apoptosis in the CD4+CD25+ T-cell fraction. PLoS One 2007;2:e146. |
|28.||Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003;4:330-6. |
|29.||Zhang Q, Qian FH, Liu H, Zhou LF, Huang M, Zhang XL, et al. Expression of surface markers on peripheral CD4+CD25high T cells in patients with atopic asthma: Role of inhaled corticosteroid. Chin Med J (Engl) 2008;121:205-12. |
|30.||Lawson JM, Tremble J, Dayan C, Beyan H, Leslie RD, Peakman M, et al. Increased resistance to CD4+CD25hi regulatory T cell- mediated suppression in patients with type 1 diabetes. Clin Exp Immunol 2008;154:353-9. |
|31.||Brusko TM, Wasserfall CH, Clare-Salzler MJ, Schatz DA, Atkinson MA. Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes. Diabetes 2005;54:1407-14. |
|32.||Zmys³owska A, Szadkowska A, Andrzejewski W, Wegner O, Wyka K, M³ynarski W, et al . [Factors affecting C-peptide level during the first year of type 1 diabetes in children]. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw 2004;10:103-11. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]
|This article has been cited by|
||Regulatory T cells increase after treatment with poly (ADP-ribose) polymerase-1 inhibitor in ischemic stroke patients
| ||Min-Young Noh,Won Moo Lee,Su-Jung Lee,Hyun Young Kim,Seung Hyun Kim,Young Seo Kim |
| ||International Immunopharmacology. 2018; 60: 104 |
|[Pubmed] | [DOI]|
||The Yin and Yang of regulatory T cell and therapy progress in autoimmune disease
| ||Yong-chao Qiao,Yan-hong Pan,Wei Ling,Fang Tian,Yin-ling Chen,Xiao-xi Zhang,Hai-lu Zhao |
| ||Autoimmunity Reviews. 2017; |
|[Pubmed] | [DOI]|
||ß-cell specific T-lymphocyte response has a distinct inflammatory phenotype in children with Type 1 diabetes compared with adults
| ||S. Arif,V. B. Gibson,V. Nguyen,P. J. Bingley,J. A. Todd,C. Guy,D. B. Dunger,C. M. Dayan,J. Powrie,A. Lorenc,M. Peakman |
| ||Diabetic Medicine. 2017; 34(3): 419 |
|[Pubmed] | [DOI]|
||Effects of royal jelly supplementation on regulatory T cells in children with SLE
| ||Asmaa M. Zahran,Khalid I. Elsayh,Khaled Saad,Esraa M.A. Eloseily,Naglaa S. Osman,Mohamd A. Alblihed,Gamal Badr,Mohamed H. Mahmoud |
| ||Food & Nutrition Research. 2016; 60(1): 32963 |
|[Pubmed] | [DOI]|
||Changes of regulatory T cells, transforming growth factor-beta and interleukin-10 in patients with type 1 diabetes mellitus: A systematic review and meta-analysis
| ||Yong-chao Qiao,Jian Shen,Xue-zhi Hong,Ling Liang,Chao-sheng Bo,Yi Sui,Hai-lu Zhao |
| ||Clinical Immunology. 2016; 170: 61 |
|[Pubmed] | [DOI]|
||T regulatory lymphocytes in type 1 diabetes: Impaired CD25 expression and IL-2 induced STAT5 phosphorylation in pediatric patients
| ||Zuzana Parackova,Jana Kayserova,Klara Danova,Kristyna Sismova,Eva Dudkova,Zdenek Sumnik,Stanislava Kolouskova,Jan Lebl,Katerina Stechova,Anna Sediva |
| ||Autoimmunity. 2016; : 1 |
|[Pubmed] | [DOI]|
||The immunomodulatory effects of human mesenchymal stem cells on peripheral blood mononuclear cells in ALS patients
| ||Min-Soo Kwon,Min-Young Noh,Ki-Wook Oh,Kyung-Ah Cho,Byung-Yong Kang,Kyung-Suk Kim,Young-Seo Kim,Seung H. Kim |
| ||Journal of Neurochemistry. 2014; : n/a |
|[Pubmed] | [DOI]|
||Regulatory T cells with CD62L or TNFR2 expression in young type 1 diabetic patients: relation to inflammation, glycemic control and micro-vascular complications
| ||Mona H. El-Samahy,Amira A.M. Adly,Eman A. Ismail,Nouran Yousef Salah |
| ||Journal of Diabetes and its Complications. 2014; |
|[Pubmed] | [DOI]|
||Extension of the CD4+Foxp3+CD25-/lowregulatory T-cell subpopulation in type 1 diabetes mellitus
| ||András Zóka,Gábor Barna,Anikó Somogyi,Györgyi Muzes,Ágnes Oláh,Zahra Al-Aissa,Orsolya Hadarits,Katalin Kiss,Gábor Firneisz |
| ||Autoimmunity. 2014; : 1 |
|[Pubmed] | [DOI]|
||Prognostic value of regulatory T cells in newly diagnosed chronic myeloid leukemia patients
| ||Asmaa M. Zahran,Hosny Badrawy,Abeer Ibrahim |
| ||International Journal of Clinical Oncology. 2013; |
|[Pubmed] | [DOI]|