1.New insights into the immunopathogenesis of systemic lupus erythematosus: the role of T follicular helper cells.
Huijuan MA ; Suigui WAN ; Changqing XIA
Chinese Medical Journal 2014;127(19):3496-3502
OBJECTIVETo review the development of T follicular helper (TFH) cells and their role in systemic lupus erythematosus (SLE) pathogenesis, the effect of dendritic cells (DCs) on TFH cells in SLE, as well as the potential use of TFH cells as a new therapeutic target in clinical practice.
DATA SOURCESThe data used in this review were retrieved mainly from the PubMed database (1989-2013). The terms used in the literature search were "T follicular helper cells," "systemic lupus erythematosus," and "dendritic cells."
STUDY SELECTIONRelevant publications about the TFH cells development, the interaction between the TFH cells and the DCs, and the clinical applications of TFH cells were identified, retrieved, and reviewed.
RESULTSTFH cells, a novel distinct CD4+ T cell subset, are specialized in providing help to B cells in the formation of germinal centers (GCs) and long-term protective humoral immune responses. The development of TFH cells from naïve CD4+ T cell is a multistep process. As the pivot of immunoregulation, DCs are indispensable for TFH cells generation. In addition to receptor-ligand interactions between TFH cells and DCs, the cytokines secreted by DCs are also necessary for TFH cell generation. TFH cell dysregulation has been implicated in the development of SLE. More evidence from animal models of SLE and SLE patients suggests that TFH cells are necessary for pathogenic autoantibody production. Therefore, therapeutically targeting TFH cells can be a promising approach to treat antibody-mediated autoimmune diseases including SLE.
CONCLUSIONTFH cells play a critical role in the pathogenesis of SLE, making them attractive therapeutic targets in clinical practice.
Autoantibodies ; immunology ; Dendritic Cells ; immunology ; Humans ; Lupus Erythematosus, Systemic ; immunology ; T-Lymphocytes, Helper-Inducer ; immunology
2.Advances of studies on T follicular helper cells.
Hua-Quan WANG ; Zong-Hong SHAO
Journal of Experimental Hematology 2009;17(5):1384-1389
T follicular helper cells (TFH cells) provides a helper function to B cells. It is one of the most important subsets of effector T cells in lymphoid tissues. The features of TFH cells include chemokine receptor expression (CXCR5), location/migration (B cell follicles), and function (B cell help). TFH cells produce a "helper" cytokine-IL-21, which can stimulate B cells to differentiate into Ab-forming cells through IL-21R. Dysregulation of TFH cell function likely contributes to the pathogenesis of immune-related diseases. In this article, the discovery of CXCR5 and TFH cells, origin of TFH cells, cytokines related with TFH cell function, migration and location of TFH effector cells and memory cells as well as dysregulation of TFH cell function and related diseases were reviewed.
Humans
;
Interleukins
;
immunology
;
Receptors, CXCR5
;
immunology
;
T-Lymphocytes, Helper-Inducer
;
immunology
3.Progress of pathogenesis and clinical treatment of Hashimoto's thyroiditis.
Qing GAO ; Li-Xin JIAN ; Jin-Guo XU ; Wen-Lin LI ; Zhi-Wei JIAN ; Su-Hua PAN
China Journal of Chinese Materia Medica 2012;37(20):3003-3006
Hashimoto's thyroiditis (HT) is a autoimmune disease that is highly incident year by year. Its clinical manifestations are alternative hyperthyroidism or hypothyroidism, relatively high Th1, excessively low Th2 and constantly increasing TGAb and TMAB. Currently, the disease is still difficult to be cured, and instable thyroid function makes it harder to be treated. Therefore, this essay makes a summary analysis on domestic and foreign studies on HT's pathogenesis, clinical manifestations and treatment, resulting that pure supplement or immunosuppressive therapy is hard to achieve notable efficacy, while existing traditional Chinese medicines could only mitigate clinical symposiums but did not reduce inflammation. Therefore, to look for methods and drugs for adjusting immunity imbalance by decreasing Th1 cell factors and increasing Th2 cell factors is significant to HT treatment to some extent.
Animals
;
Autoantibodies
;
immunology
;
Female
;
Humans
;
T-Lymphocytes, Helper-Inducer
;
immunology
;
Thyroiditis, Autoimmune
;
drug therapy
;
immunology
;
pathology
4.The changes of circulating follicular regulatory T cells and follicular T helper cells in children immune thrombocytopenia.
Yajie CUI ; Yujie GUAN ; Wei LIU ; Yan'ge LI ; Huixia LI ; Mingfa GUO
Chinese Journal of Hematology 2014;35(11):980-984
OBJECTIVETo investigate the changes and roles of follicular regulatory T cells (Tfr) and follicular T helper cells (Tfh) in the pathogenesis of children immune thrombocytopenia (ITP).
METHODS32 untreated ITP patients, as well as 20 healthy controls were enrolled in this study. The proportion of circulating Tfr and Tfh cells were determined by flow cytometry; real-time PCR was performed to detect the expression of transcription factors and regulatory factors of Bcl-6, c-Maf, Blimp-1 and PD-1 mRNA; ELISA was used to detect plasma concentration of IL-2, IL-6, IL-10 and IL-21.
RESULTS(1)The proportion of Tfh cells were significantly higher (P<0.05), while the Tfr cells and the ratio of tfr/Tfh cells in ITP patients were significantly lower than that in health controls (P<0.05); (2)Correlation analysis showed that the Tfr cells and the ratio of Tfr/Tfh were positively correlated with the platelet counts and negatively with the levels of PA-IgG, while the proportion of Tfh cells was positively correlated with the levels of PA-IgG and negatively with the platelet counts in peripheral blood; (3)Transcription levels of Bcl-6 and c-Maf mRNA in CD4(+) T lymphocytes cells were significantly elevated, the Blimp-1 mRNA in CD4(+) cells and PD-1 mRNA levels of Treg were lower in ITP patients in comparison with healthy controls; (4)The higher Plasma concentration of IL-21, and lower concentration of IL-2 were found in ITP patients.
CONCLUSION(1)The lower proportion of Tfr cells and higher proportion of Tfh cells, as well as the abnormal ratio of Tfr/Tfh might account for the decreased platelet counts to be further involved in the immunological pathogenesis of children ITP; (2)The changes of plasma cytokines IL-2, IL-21 in microenvironment and the over-expression of Bcl-6 mRNA, c-Maf mRNA and the lower-expression of Blimp-1 mRNA in CD4(+) T cells, and over-expression of PD-1 mRNA in Treg cells might be account for the abnormal ratios of Tfr/Tfh cells in ITP patients.
Cell Movement ; Child ; Humans ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; T-Lymphocytes, Helper-Inducer ; immunology ; T-Lymphocytes, Regulatory ; immunology
5.Mucosal dendritic cells shape mucosal immunity.
Sun Young CHANG ; Hyun Jeong KO ; Mi Na KWEON
Experimental & Molecular Medicine 2014;46(3):e84-
Dendritic cells (DCs) are key modulators that shape the immune system. In mucosal tissues, DCs act as surveillance systems to sense infection and also function as professional antigen-presenting cells that stimulate the differentiation of naive T and B cells. On the basis of their molecular expression, DCs can be divided into several subsets with unique functions. In this review, we focus on intestinal DC subsets and their function in bridging the innate signaling and adaptive immune systems to maintain the homeostasis of the intestinal immune environment. We also review the current strategies for manipulating mucosal DCs for the development of efficient mucosal vaccines to protect against infectious diseases.
Animals
;
Dendritic Cells/*immunology/metabolism
;
Humans
;
Immunity, Mucosal
;
Intestinal Mucosa/cytology/*immunology
;
T-Lymphocytes, Helper-Inducer/immunology
6.Study of Th cell subsets in bone marrow of myelodysplastic syndromes patients.
Xiu-li WANG ; Zong-hong SHAO ; Cheng YAO ; Guang-sheng HE ; Hong LIU ; Jun SHI ; Jie BAI ; Yan-ran CAO ; Mei-feng TU ; Hua-quan WANG ; Li-min XING ; Juan SUN ; Hai-rong JIA ; Chong-li YANG
Chinese Journal of Hematology 2005;26(12):743-745
OBJECTIVETo study the quantity and ratio of Th1, Th2 cells in the bone marrow of myelodysplastic syndromes (MDS) patients, and to evaluate the correlation between the ratio of the blast cells and the number of the Th1 cells in the bone marrow of MDS patients.
METHODSBy FACS, the quantity and ratio of IFN-gamma producing CD4(+) T cell (Th1) and IL-4 producing CD4(+) T cell (Th2) cells in the bone marrow were detected in 21 MDS patients, 18 normal controls and 13 severe aplastic anemia (SAA) patients respectively. The karyotypes of 18 MDS patients and 15 normal controls were assayed. The correlation between the ratio of the blast cells in the bone marrow and the number of the Th1 cells in the MDS patients were analyzed.
RESULTSThe percentages of Th1 cells, Th2 cells and ratio of Th1/Th2 in the bone marrow of normal controls were (0.48 +/- 0.10)%, (0.24 +/- 0.19)% and 2.31 +/- 0.76 respectively, while those of the MDS patients were (0.36 +/- 0.11)%, (0.76 +/- 0.35)% and 0.51 +/- 0.13. The percentage of Th1 cells of patients with MDS was reduced and the Th1/Th2 ratio was significantly lower than that of normal controls (P < 0.01). Those of the patients with SAA were (4.75 +/- 0.49)%, (0.40 +/- 0.28)% and 26.5 +/- 8.79 respectively, their Th1 cells and Th1/Th2 ratio were markedly higher than those of normal controls (P < 0.01). In all of the 15 normal controls the karyotypes were normal, but that of MDS patients was (50.00 +/- 0.10)%. The lower ratio of the Th1 cells in the bone marrow of the patients with MDS and the AML which progressed from MDS was negatively correlated with the higher percentage of the blast cells (r = -0.563, P < 0.01).
CONCLUSIONS(1) The immune function of T lymphocytes in MDS is abnormal: the balance between Th1 and Th2 cells is broken. (2) With descending of the number of Th1 cells in the bone marrow of the MDS patients, the disease is progressing to leukemia.
Adult ; Aged ; Bone Marrow ; immunology ; Female ; Humans ; Karyotyping ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; immunology ; T-Lymphocytes, Helper-Inducer ; immunology
7.Determination of Th9 cells and IL-9 in children with Mycoplasma pneumoniae infection.
Jian-Yong WANG ; Jing ZHENG ; Hai-Yan XING ; Xiu-Hong JIA
Chinese Journal of Contemporary Pediatrics 2015;17(4):308-311
OBJECTIVETo investigate the clinical significance of T helper type 9 (Th9) cells and interleukin-9 (IL-9) in children suffering from Mycoplasma pneumoniae (MP) infection.
METHODSA total of 86 children who were diagnosed with MP infection between January 2013 and June 2014 were classified into upper respiratory infection (URI) group (n=29), mild MP pneumonia (MPP) group (n=32) and severe MPP group (n=25). Twenty-eight healthy children were used as the control group. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation, and the percentage of Th9 cells in peripheral blood was measured by flow cytometry. Serum IL-9 level was determined using ELISA.
RESULTSThe URI, mild MPP, and severe MPP groups had significantly higher percentages of Th9 cells and IL-9 levels than the control group (P<0.05); the mild MPP and severe MPP groups had significantly higher percentages of Th9 cells and IL-9 levels than the URI group (P<0.05), and the two indices were significantly higher in the severe MPP group than in the mild MPP group (P<0.01).
CONCLUSIONSChildren with MP infection have an elevated percentage of Th9 cells and IL-9 expression, both of which are positively correlated with the severity of the disease. It can be predicted that Th9 cells and IL-9 can be used as evaluation indicators for the progression and outcome of children with MP infection.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Interleukin-9 ; blood ; Male ; Pneumonia, Mycoplasma ; immunology ; T-Lymphocytes, Helper-Inducer ; immunology
8.Role of antigen-specific T cell-mediated immune response in coronary heart disease.
Hua ZHENG ; Wen-yan LAI ; Yan TU
Journal of Southern Medical University 2008;28(8):1398-1399
UNLABELLEDTo investigate the effect of immune response mediated by the T cells stimulated with the specific antigen (oxidized low-density lipoprotein, oxLDL) on plaque stability in coronary heart disease.
METHODSThis study involved 20 patients with acute myocardial infarction (AMI), 34 with unstable angina pectoris (UAP), 27 with stable angina pectoris (SAP) and 22 healthy control subjects. With MTS/PMS colorimetric assay, the T cells from all the subjects were tested for proliferative response to stimulation by 5 microg/ml oxLDL and 5 microg/ml low-density lipoprotein (LDL). Interferon-gamma (IFN-gamma) concentration in the proliferative response of the T cells was measured with enzyme-linked immunosorbent assay (ELISA).
RESULTSThe proliferative response of the T cells elicited by 5 microg/ml oxLDL stimulation was significantly higher in the AMI and UAP groups than in the SAP and control groups (P<0.05). Similarly, IFN-gamma concentration in the proliferative response of the T cells to 5 microg/ml oxLDL stimulation was significantly higher in the former two groups (P<0.05). In the AMI and UAP groups, 5 microg
CONCLUSIONThe immune response mediated by the T cells to specific antigen stimulation, especially the immune response mediated by T helper type 1 (Th1) cells secreting IFN-gamma, may play an important role in the plaque instability and the occurrence of acute coronary syndrome.
Aged ; Coronary Disease ; immunology ; Female ; Humans ; Interferon-gamma ; secretion ; Lipoproteins, LDL ; immunology ; Male ; Middle Aged ; T-Lymphocytes ; immunology ; metabolism ; T-Lymphocytes, Helper-Inducer ; immunology ; metabolism
9.Advances of research on abnormality of cell immunity in idiopathic thrombocytopenic purpura: review.
Journal of Experimental Hematology 2006;14(5):1045-1048
It was long believed that platelets are prematurely destroyed in the reticuloendothelial system by platelet autoantibodies in idiopathic thrombocytopenic purpura. However, humoral mechanisms cannot account for all observations made in this disorder, and it is increasingly evident that cellular mechanisms contribute to platelet destruction. In this review the tolerance of T cell, abnormality of T cell apoptosis, abnormal activation of T cells, T cell subtype and its function changes, and T cell-mediated cytotoxicity were summarized.
Apoptosis
;
immunology
;
Autoantibodies
;
immunology
;
Humans
;
Immune Tolerance
;
Immunity, Cellular
;
immunology
;
Purpura, Thrombocytopenic, Idiopathic
;
immunology
;
T-Lymphocyte Subsets
;
immunology
;
T-Lymphocytes
;
immunology
;
pathology
;
T-Lymphocytes, Cytotoxic
;
immunology
;
T-Lymphocytes, Helper-Inducer
;
immunology
10.The enhancing effect of "Xuebijing injection" on lipopolysaccharide-induced apoptosis of regulatory T cells and mediation of polarization of helper T cells.
Xin-Gui DAI ; Yong-Ming YAO ; Yu-Hang AI ; Yan YU
Chinese Journal of Burns 2009;25(2):106-110
OBJECTIVETo investigate the enhancing effect of Chinese medicine-Xuebijing injection on lipopolysaccharide (LPS) -induced apoptosis of CD4+ CD25+ regulatory T cells (Tregs) and polarization of helper T cells (Th).
METHODSCD4+ CD25+ Tregs collected from rat spleen in vitro by immunomagnetic beads assay were divided into the control group, anti-CD3/CD28 group, anti-CD3/CD28 + LPS group, anti-CD3/CD28 + "Xuebijing injection" group and anti-CD3/CD28 + LPS + "Xuebijing injection" group. Tregs apoptosis rate and expression of winged helix transcription factor (Foxp3) in Tregs were detected by flow cytometry on 3rd post culture day. CD4+ CD25- T cells were co-cultured with CD4+ CD25- Tregs (1:1) for 68 hours with canavalin A stimulation. Interferon gamma (gamma-IFN), interleukin (IL)-4 and IL-17 in supernatants, which respectively was secreted by Th1, Th2 and Th17, were measured by ELISA.
RESULTSTregs apoptosis rate of anti-CD3/CD28 + LPS + "Xuebijing injection" group (45.1 +/- 2.7%) was significantly higher than that of anti-CD3/CD28 + LPS group (29.4 +/- 1.6%, P < 0.01). Meanwhile, Foxp3 expressions in Tregs in above 2 groups were 95 +/- 9 and 140 +/- 18 respectively, showing statistically significant difference between them (P < 0.01). Gamma-IFN levels secreted in anti-CD3/CD28 + LPS + "Xuebijing injection" group were significantly higher than those in anti-CD3/CD28 + LPS group (P < 0.01), while IL-4 levels had an opposite tendency compared with gamma-IFN (P < 0.05), resulting in a marked increase in the ra- tio of gamma-IFN/IL-4 in anti-CD3/CD28 + LPS + "Xuebijing injection" group (P < 0.01). In anti-CD3/ CD28 + "Xuebijing injection" group, IL-17 secretion levels were significantly decreased compared with anti-CD3/CD28 group (P < 0.05).
CONCLUSIONSActivation of CD4+ CD25+ Tregs induced by LPS may mediate Th1 shift to Th2 response. "Xuebijing injection" can effectively regulate immune function of T cells, increase the LPS-induced apoptosis of CD4+ CD25+ Tregs as well as enhance the polarization of Th2 to Th1, thereby abating the suppressive state of cell-mediated immunity.
Animals ; Apoptosis ; Drugs, Chinese Herbal ; pharmacology ; Endotoxins ; Lipopolysaccharides ; Male ; Rats ; Rats, Wistar ; T-Lymphocytes, Helper-Inducer ; drug effects ; immunology ; T-Lymphocytes, Regulatory ; drug effects ; immunology