Bile Ducts, Intrahepatic ; metabolism ; Humans ; Interleukin-2 Receptor alpha Subunit ; metabolism ; Liver ; metabolism

BACKGROUNDSystemic sclerosis (SSc) is an autoimmune disease that has three major components: inflammation, fibrosis, and vasculopathy. T-helper 17 cell (Th17) and regulatory T cell (Treg) are considered to be critical for autoimmune disease pathogenesis. The role of Th17 and Treg in SSc is still unclear. The aim of this study was to detect the presence of Th17s and CD4(+)CD25(+) Tregs in peripheral blood samples from SSc patients and to investigate the possible roles of these two T cell subsets in SSc pathogenesis.

METHODSTh17s (CD4 and IL-17 positive) and CD4(+)CD25(+) Tregs (CD4, CD25 and Foxp3 positive) in the peripheral blood mononuclear cells of 53 SSc patients and 27 healthy controls were counted by flow cytometry. The differences between SSc and control patients were analyzed. Clinical parameters, including disease duration, duration of the second symptoms, Modified Rodnan Skin Score (MRSS), anti-topoisomerase I antibody, anti-U1 ribonucleoprotein (RNP) antibody, systemic involvements, pulmonary function test (PFT) and high resolution computed tomography (HRCT) score were prospectively collected following EUSTAR (EULAR scleroderma trial and research group) protocols. The correlations between the experimental and clinical data were investigated.

RESULTSThe ratio of Th17 in SSc patients was significantly elevated compared to healthy controls (8.74% vs. 4.41%, P < 0.001). The amount of Th17 was positively correlated with disease duration (R = 0.531, P = 0.013) and duration of the second symptoms (R = 0.505, P = 0.023). The ratio of CD4(+)CD25(+) Treg in SSc patients also significantly differed from the healthy controls (3.04% vs. 2.24%, P = 0.018). Elevated Tregs were more frequently observed in patients with a high interstitial lung disease (ILD) score on computed tomography (24/36) compared with patients with normal ILD scores (4/12, P = 0.043). Elevated Tregs were also more often observed in patients with low carbon monoxide diffusing capacity (DLCO) (24/34) compared with patients with normal DLCO (4/11, P = 0.042).

CONCLUSIONST cell abnormalities are remarkable in systemic sclerosis. Th17s proliferate and their numbers increase with lengthened disease duration. Th17s might participate in both inflammation and fibrosis by secreting IL-17. CD4(+)CD25(+) Tregs also proliferate in SSc and may play important roles in promoting fibrosis.

CD4-Positive T-Lymphocytes ; metabolism ; Cells, Cultured ; Flow Cytometry ; Humans ; Interleukin-2 Receptor alpha Subunit ; metabolism ; Scleroderma, Systemic ; immunology ; metabolism ; T-Lymphocytes, Regulatory ; immunology ; metabolism ; Th17 Cells ; metabolism

BACKGROUNDTraumatic brain injury (TBI) is a life-threatening disease worldwide. Regulatory T cells (Treg cells) were involved in the immunological system in central nervous system. It is defined as a subpopulation of CD4 + cells that express CD25 and transcription factor forkhead box P3. The level of circulating Treg cells increases in a variety of pathologic conditions. The purpose of this study was to uncover the role of circulating Treg cells in TBI.

METHODSA clinical study was conducted in two neurosurgical intensive care units of Tianjin Medical University General Hospital and Second Hospital of Tianjin Medical University (Tianjin, China). Forty patients and 30 healthy controls were recruited from August 2013 to November 2013. Circulating Treg cells was detected on the follow-up period of 1, 4, 7, 14, and 21 days after TBI. Blood sample (1 ml) was withdrawn in the morning and processed within 2 h.

RESULTSThere was no significant difference in the level of circulating Treg cells between TBI patients and normal controls during follow-up. TBI patients exhibited higher circulating Treg level than normal controls on the 1 st day after TBI. Treg level was decreased on the 4 th day, climbed up on the 7 th day and peaked on 14 th day after TBI. Treg cells declined to the normal level on 21 th day after TBI. The level of circulating Treg cells was significantly higher in survival TBI patients when compared to nonsurvival TBI patients. TBI patients with improved conditions exhibited significantly higher circulating Treg level when compared to those with deteriorated conditions. The circulating Treg level was correlated with neurologic recovery after TBI. A better neural recovery and lower hospital mortality were found in TBI patients with circulating Treg cells more than 4.91% in total CD4 + mononuclear cells as compared to those with circulating Treg cells less than 4.91% in total CD4 + mononuclear cells in the first 14 days.

CONCLUSIONSThe level of circulating Treg cells is positively correlated with clinical outcome of TBI. The level of Treg cells predicts the progress for TBI patients and may be a target in TBI treatment.

Adult ; Brain Injuries ; immunology ; CD4 Antigens ; metabolism ; Female ; Flow Cytometry ; Forkhead Transcription Factors ; metabolism ; Humans ; Interleukin-2 Receptor alpha Subunit ; metabolism ; Male ; Middle Aged ; T-Lymphocytes, Regulatory ; metabolism

Cell Membrane ; metabolism ; Clathrin ; metabolism ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; metabolism ; Endocytosis ; HeLa Cells ; Humans ; Interleukin-2 Receptor alpha Subunit ; metabolism

OBJECTIVES(1) To evaluate the prevalence, phenotypes and suppressive function of CD4+CD25+ regulatory T cells (Tregs) among the in peripheral blood mononuclear cells (PBMCs) and tumor-infiltration lymphocytes (TILs) from hepatocellular carcinoma (HCC) patients and patients with chronic hepatitis B. (2) To investigate the correlation between the frequency of CD4+CD25+ Tregs and clinical characteristics of HCC patients.

METHODSPBMCs and TILs in 18 HCC patients, 10 chronic hepatitis B (CHB) patients and 15 healthy donors were evaluated for the phenotypes of CD4+CD25+ Tregs and the proportion of CD4+CD25+ Tregs as a percentage of the total CD4+ cells, by flow cytometric analysis with three or four color staining. The relationship between the frequency of CD4+CD25+ Tregs and tumor TNM stages was analyzed. The CD4+CD25+ Tregs and CD4+CD25- T cells were isolated from PBMC of HCC patients and donors. The suppressive function of CD4+CD25+ Tregs was analyzed.

RESULTSThe percentages of CD4+CD25+ Tregs of the HCC patients (6.38% +/- 6.30%) and CHB patients (4.29% +/- 1.82%) were significantly higher than those of the healthy donors (1.58% +/- 0.55%, P less than 0.01). Among the TILs, the percentage of CD4+CD25+ Tregs was higher (t = 4.39, P < 0.01). There were significant differences in the prevalence of CD4+CD25+ Tregs in early and advanced stage HCCs (stage II vs. III, P less than 0.05; stage II vs. IV P < 0.01). The proliferative capacity of CD4+CD25- T cells was inhibited by the presence of CD4+CD25+ T cells in a dose-dependent manner where the level of suppression was correlated to the ratio of the two-cell populations.

CONCLUSIONThese results suggest that the increase in frequency of CD4+CD25+ Tregs might play a role in the suppression of the immune response against HCC, which may contribute to the HCC cells that escaped from immunological surveillance.

Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; Female ; Humans ; Interleukin-2 Receptor alpha Subunit ; Liver Neoplasms ; metabolism ; Male ; Middle Aged ; T-Lymphocytes, Regulatory ; immunology ; Young Adult

OBJECTIVETo investigate the CD25 expression in patients with acute myeloid leukemia (AML) and its significance.

METHODSClinical data of 168 newly diagnosed AML patients (except APL) were collected. The expression of CD25 in AML patients and its clinical characteristics were retrospectively analyzed.

RESULTSThe leukemia cells of 29 out of 168 cases (17.26%) expressed CD25 antigen. Most of CD25 positive AML patients were occurred in patients with unfavourable or normal karyotype, higher WBC and Plt count at diagnosis and higher percentage of blasts in peripheral blood and bone marrow. Compared with CD25(-) AML patients, CD25(+) AML patients had lower CR rate (the CR rate of 1 course of treatment were 49.02% and 16.00%, respectively, P < 0.05, the CR rate of 2 courses of treatment were 74.60% and 46.67%, respectively, P < 0.05), and the OS time of CD25(+) AML patients were obviously shorter (P < 0.05). The OS in CD25(+) AML patients with unfavorable karyotype were not significantly different from that in patients with intermediate karyotype (P < 0.05).

CONCLUSIONThe CD25(+) AML patients have some typical clinical features, and the expression of CD25 in AML is an risk factor independent of the chromosome karyotype in terms of low complete remission rate and short survival time.

Bone Marrow ; Humans ; Interleukin-2 Receptor alpha Subunit ; genetics ; metabolism ; Karyotype ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Prognosis ; Remission Induction ; Retrospective Studies

OBJECTIVETo screen and characterize the short peptides which bind specifically to interleukin-2 (IL-2) receptor alpha chain (IL-2Ralpha) for acquisition of small antagonists for blocking the binding of IL-2 with IL-2Ralpha.

METHODS12-mer phage displayed peptide library was screened with the target cells of MT-2 cells which expressed IL-2Ralpha at high levels. The binding phage clones were eluted by anti-IL-2Ralpha monoclonal antibody. After 3 rounds of screening, the positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, and the amino acid sequences of the positive clones were deduced from the DNA sequences.

RESULTSSeven positive clones were screened out of the 17 phage clones bound to MT-2 cells. The positive clone M15 could bind specifically to MT-2 cell and PHA-activated peripheral blood monouclear cells. Amino acid sequence analysis identified 6 sequences, all of which contained hydrophilic residues, and 5 of these 6 sequences included Tyr, Phe and Leu conservative residues.

CONCLUSIONThe peptide sequences containing Tyr, Phe conservative residues identified in this study can bind to cell surface IL-2Ralpha.

Amino Acid Sequence ; Cell Line, Transformed ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunohistochemistry ; Interleukin-2 ; metabolism ; Interleukin-2 Receptor alpha Subunit ; metabolism ; Peptide Library ; Peptides ; genetics ; metabolism ; Protein Binding ; Receptors, Cell Surface ; metabolism ; T-Lymphocytes ; cytology ; metabolism

This study was aimed to explore the clinical significance of NK cell activity and serum soluble CD25 (sCD25) level in early diagnosis of the patients with secondary hemophagocytic lymphohistiocytosis (HLH). 38 suspected secondary HLH patients from June 2005 to June 2008 and 25 healthy subjects were enrolled in the study. The NK cell activity in peripheral blood was determined by a released LDH assay, The sCD25 level in serum was detected with ELISA double antibody sandwich assay. The 38 suspected secondary HLH patients were divided into diagnosed and excluded group according to HLH-2004 diagnostic criteria, The NK cell activity and sCD25 level were compared between the two groups. The results showed that 22 out of 38 suspected patients were diagnosed as secondary HLH, the NK cell activity in peripheral blood of these 22 patients was significantly lower than that of healthy control (p < 0.001), the sCD25 level in peripheral blood of these 22 diagnosed patients was higher than that of healthy control (p < 0.05). In conclusion, detection of NK cell activity and sCD25 level may be valuable in the early diagnosis of secondary HLH.
Case-Control Studies ; Early Diagnosis ; Humans ; Interleukin-2 Receptor alpha Subunit ; blood ; Killer Cells, Natural ; metabolism ; Lymphohistiocytosis, Hemophagocytic ; blood ; diagnosis ; Serum

The aim of this study was to investigate the reconstitution of CD4(+)CD25(+) T cells after haplo-identical bone marrow transplantation (hiBMT) and its correlation with graft versus host disease (GVHD) and relapse. Peripheral blood samples from 27 patients after hiBMT were harvested and the percentage and absolute counts of CD4(+)CD25(+) T cells were detected by flow cytometry. The correlations of GVHD occurrence and disease relapse with the reconstitution of CD4(+)CD25(+) T cells were analyzed. The results showed that the percentage of CD4(+)CD25(+) T cells of peripheral blood samples increased significantly after G-CSF priming. At day 30 after hiBMT, CD4(+)CD25(+) T cells were recovered to the 20% of normal level, followed by a slowly process in 3 months, and up to one half of the normal level at 180 days. There was no evidence to prove relationship between CD4(+)CD25(+) T cells and acute GVHD, while CD4(+)CD25(+) T cells were increased significantly in the chronic GVHD group. The absolute count of CD4(+)CD25(+) T cells showed no relations with relapse of leukemia during the first year after hiBMT. In conclusions, chronic but not acute GVHD was in relation to the reconstitution of CD4(+)CD25(+) T cells based on the anti-CD25 antibody therapy model for the prevention of GVHD after hiBMT. Further investigation is needed to clarify whether the relapse of leukemia after hiBMT is related to the reconstitution of CD4(+)CD25(+) T cells.
Bone Marrow Transplantation ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes ; immunology ; Graft vs Host Disease ; etiology ; Humans ; Interleukin-2 Receptor alpha Subunit ; metabolism ; Leukemia ; immunology ; surgery

As a functionally and phenotypically distinctive T cell subpopulation, CD4+CD25+ regulatory T cells are anergic and retain their ability to suppress antigen-driven response of CD4+CD25- cells in a contact-dependent manner or through a way of secreting immunosuppressive cytokines such as IL-10 and TGF-beta. Graft-versus-host disease (GVHD) is one of the major complications following allogeneic hematopoietic stem cell transplantation (HSCT). Recently, some researches on the relationship between donor CD4+CD25+ regulatory T cells and GVHD severity produced two contradictory conclusions: one is CD4+CD25+ regulatory T cells that can prevent GVHD efficiently; the other is that GVHD is associated with the increased numbers of peripheral blood CD4+CD25+ regulatory T cells. The answer to this question will provide a new idea for clinic therapy of GVHD. In this review some new research progresses in the related area, such as the CD4+CD25+ regulatory T cells, the phenotype, characteristics, immunoregulatory mechanisms of CD4+CD25+ regulatory T cells, as well as the relation of CD4+CD25+ with GVHD were presented.
CD4 Antigens ; analysis ; Graft vs Host Disease ; etiology ; immunology ; Humans ; Interleukin-2 Receptor alpha Subunit ; analysis ; T-Lymphocytes, Regulatory ; cytology ; immunology ; metabolism