2.Immune pathogenesis of IgA nephropathy and its drugable targets.
Liyu HE ; Hong LIU ; Youming PENG
Journal of Central South University(Medical Sciences) 2014;39(1):96-101
IgA nephropathy (IgAN) is recognized as the most common immune complex related to the cause of glomerulonephritis worldwide. The disease is characterized by the predominant deposition of underglycosylated IgA1 in the mesangial area of glomeruli. Dysregulation of the immune system plays an important role in the pathogenesis of IgAN. Abnormalities restricted to T lymphocytes and/or B lymphocytes activation could be a critical causative factor in the over-production of underglycosylated IgA1.
Antigen-Antibody Complex
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B-Lymphocytes
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Glomerular Mesangium
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Glomerulonephritis, IGA
;
pathology
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Humans
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Immunoglobulin A
;
chemistry
;
T-Lymphocytes
3.Changes of T-cell clonality after induction-cultivation of peripheral T lymphocytes in adoptive immunotherapy for leukemias.
Yan LIU ; Jiang-Ying GU ; Yuan OU ; Mian-Yang LI ; He WANG ; Xian JIN ; Xiu-Yan TAO ; Zhao-Li LIU ; Xing-Fan MA ; Xiu-Li WANG ; Si-Kun MA ; Rui KANG ; Peng CAI ; Chun-Rong TONG ; Ping ZHU
Journal of Experimental Hematology 2009;17(3):621-626
This study was purposed to analyze the changes of T-cell clonality after induction of peripheral T lymphocytes by autogenous DC and cytokines in the preparation of adoptive immunotherapy for leukemias. The bone marrow and peripheral blood from 21 leukemia patients at remission stage after treatment and subjected to adoptive immunotherapy were collected. Their DCs and T-cells were stimulated with cytokines and then were mixed to activate T-cells. T-cell receptor beta variable region (TCRBV) families were amplified by RT-PCR, and genescan method and sequencing of the PCR products were used to observe the clonality changes of T-cells before and after the induction and cultivation of T-cells. The flow cytometry was used to identify CD3(+), CD4(+), CD8(+), CD3(+)CD56(+) and CD4(+)CD25str(+)FOXP3(+) cells to disclose the ratio change of cytotoxic T lymphocytes (CTL), helper T-cells, regulatory T-cells and NK T-cells before and after induction and cultivation of T-cells. The results showed that in the 21 patients, most of the 24 TCRBV families presented as oligoclonal distribution on genescan, several families were not expressed, and only a few families remained polyclonal. TCRBV24 was found to be oligoclonal in all of the 21 patients. DNA sequence analysis of TCRBV24 revealed a common motif of VAG in CDR3 in 3 cases and a common motif of GGG in CDR3 in 2 cases. In patient 5, both TCRBV 24 and TCRBV8 contained the same motif of GGG in CDR3. The identical motif in these patients may suggest that these T-cells recognize the same antigen. The peripheral lymphocytes demonstrated recovery of clonal profile on genescan from oligoclonal profile and absence of several families before the induction and cultivation to typical polyclonal profile in all TCRBV families after the induction by DC and cytokines for 13 days. After the induction and cultivation, the number of lymphocytes increased to 3.38 +/- 1.20 times. CD3(+), CD4(+), CD8(+), CD3(+)CD56(+) and CD4(+)CD25str(+)FOX P3(+) cells were 71.1 +/- 11.8%, 26.7 +/- 11.4%, 35.7 +/- 12.9%, 3.1 +/- 1.6% and 0.12 +/- 0.1% respectively before the induction and cultivation, and changed to 95.4 +/- 3.2% (p < 0.01), 27.0 +/- 13.1% (p > 0.01), 55.5 +/- 13.8% (p < 0.01), 9.8 +/- 6.1% (p < 0.01) and 0.22 +/- 0.18% (p < 0.01) respectively after the induction and cultivation. It is concluded that the major action of this induction and cultivation method on T-lymphocytes in vitro is the promotion of CTL and NK T-cell proliferation. In leukemic patients at the remission stage, the TCRBV profile is characterized by the oligoclonal proliferation of T-lymphocytes. Several proliferated clones may have the same motif in CDR3, suggesting the recognition of the same antigen by these lymphocyte clones. Cytokine induction and co-culture with autogenous DCs can stimulate the T-lymphocytes to recover their immunocompetence as manifested by the polyclonal profile and the proliferation of CTL and NK-T cells.
Adolescent
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Adult
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Aged
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Child
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Female
;
Genes, T-Cell Receptor beta
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Humans
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Immunotherapy, Adoptive
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Leukemia
;
genetics
;
immunology
;
therapy
;
Lymphocyte Activation
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Male
;
Middle Aged
;
T-Lymphocytes
;
chemistry
;
cytology
;
immunology
;
T-Lymphocytes, Cytotoxic
;
immunology
;
T-Lymphocytes, Regulatory
;
chemistry
;
immunology
;
Young Adult
4.Effect of oral scorpio and scolopendra powder on T-cell subsets in peripheral blood and intestine from rats with collagen induced arthritis.
Shaomin CHENG ; Haimei ZHAO ; Zhiqin ZUO ; Yanhui WANG ; Yuesheng WANG ; Duanyong LIU
China Journal of Chinese Materia Medica 2011;36(5):633-635
OBJECTIVETo observe effect of oral scorpio and scolopendra powder on T-cell subsets in peripheral blood and intestine from rats with collagen induced arthritis (CIA).
METHOD60 rats were randomly divided into 6 groups: normal control group, model control group, low-dose scorpio and scolopendra group, middle-dose scorpio and scolopendra group, high-dose scorpio and scolopendra group, and type II collagen group. Rat's rheumatoid arthritis was induced by collagen II (C II). Level of T-cell subsets from peripheral blood and intestine was measured by flow cytometry.
RESULTCD4+ T cellular level was obviously increased (P < 0.05 or P < 0.01) or kept increased tendency in peripheral blood and intestine from the model group compared with that of the normal group, while the ratio of CD4+/CD8+ in intestine was obviously descent but the contrary in peripheral blood (P < 0.05 or P < 0.01). CD4+, CD8+ T cellular level in intestine were obviously descent and the ratio of CD4+ /CD8+ increased in all treated groups when compared with in the model group (P < 0.05 or P < 0.01). However, CD4+ T cellular level and the ratio of CD4+/CD8+ in peripheral blood were remarkablely decreased.
CONCLUSIONThe mechanism that scorpio and scolopendra could treat rat's rheumatoid arthritis may be regulating balance of T-lymphocyte subsets in peripheral blood and intestine.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Arthritis, Experimental ; immunology ; Arthritis, Rheumatoid ; immunology ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Female ; Intestinal Mucosa ; immunology ; Medicine, Chinese Traditional ; Rats ; Rats, Wistar ; Scorpions ; chemistry ; T-Lymphocyte Subsets ; drug effects ; immunology
5.Influence of different processing methods on Angelica sinensis polysaccharides from same origin.
Jieli LV ; Hongli CHEN ; Jinao DUAN ; Hui YAN ; Yuping TANG ; Bingsheng SONG
China Journal of Chinese Materia Medica 2011;36(7):846-849
OBJECTIVETo study the influences of different processing methods on the content of Angelica sinensis polysaccharides (APS) from the same origin.
METHODThe contents of neutral polysaccharides and acidic polysaccharides in various samples of A. sinensis were determined by phenol-sulfuric acid and carbazole-sulfuric acid method, respectively. The proliferation ability of lymphocyte was detected by MTT method after the cells were cultured with different concentrations of APS from two samples processed by different methods.
RESULTThe different processing methods had different effects on the contents of polysaccharide. The maximum content of APS (26.03%) was found in the sample processed by microwave drying medium-fired, but the minimum content of APS (2.25%) was found in the sample processed by vacuum drying at 50 TC. Furthermore, the APS (high concentration group, P < 0.01) processed by microwave drying medium-fired could both accelerate proliferation of spleen lymphocytes directly and increase proliferation of T cells of mice induced by Con A. However, the APS processed by far-infrared drying did not show conspicuous immune enhancement activity.
CONCLUSIONDifferent processing methods have different effects on the contents of APS and the proliferation ability of lymphocytes.
Angelica sinensis ; chemistry ; Animals ; Cell Proliferation ; drug effects ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; Mice ; Polysaccharides ; chemistry ; isolation & purification ; pharmacology ; Spleen ; cytology ; T-Lymphocytes ; cytology ; drug effects
6.Effects of three Chinese herbal antidotes (Herba artemisiae annuae, Herba hedyotis diffusae and Rhizoma cimicifugae) and their different combinations on regulated on activation normal T cell expressed and secreated expression in MRL/lpr mice.
Yong-sheng FAN ; Cheng-ping WEN ; Zhi-jun XIE
Chinese Journal of Integrated Traditional and Western Medicine 2010;30(12):1306-1309
OBJECTIVETo explore the effects of three Chinese herbal antidotes, i.e. Herba Artemisiae annuae (A), Herba Hedyotis diffusae (H) and Rhizoma Cimicifugae (C), all were ingredients of Jiedu Quyu Ziyin Recipe, for adjusting the regulated on activation normal T cell expressed and secreated (RANTES), gene expression in serum and renal tissue of MRL/lpr mice.
METHODSFifty-four MRL/lpr mice were randomized into 9 groups, with 6 in each, and intragastrically infused with A, H, C, A+H, H+C, A+C, A+H+C (all in dosage-form of decoction), prednisone suspension and physiological saline, respectively for 12 weeks. RANTES expression in serum and renal tissue of animals were detected with ELISA and RT-PCR at the end of the study.
RESULTSLevels of RANTES expression was significantly reduced in the prednisone treated group after treatment. Excepting no significant change being observed in the groups treated with A and C, the changes in the other groups were all milder than those in the group treated with A+H+C.
CONCLUSIONChinese herbal antidotes A, H and C in combination can significantly inhibit the RANTES expression in serum and renal tissue of MRL/lpr mice.
Animals ; Artemisia annua ; chemistry ; Chemokine CCL5 ; blood ; metabolism ; Cimicifuga ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hedyotis ; chemistry ; Kidney ; metabolism ; Mice ; Mice, Inbred MRL lpr ; T-Lymphocytes ; immunology ; metabolism
7.Expression of co-receptor on different T lymphocytes subpopulations after effective HAART.
Dan LI ; Nan-ping WU ; Armin BADER ; Stefan HOXTERMANN ; Norbert BROCKMEYER
Journal of Zhejiang University. Medical sciences 2003;32(2):97-100
OBJECTIVETo measure CCR5 and CXCR4 chemokine receptor expression on CD4 and CD8 T cells in HIV-1 infection and to relate levels to the distribution of CD45RO memory and CD45RA-naive subsets after effective HAART.
METHODSFour-color cytofluorometry with appropriate conjugated monoclonal antibodies (mAbs) was performed to define CD45RA and CD45RO subsets of CD4 and CD8 T cells and measure the expression of CCR5, CXCR4 in blood from 43 received HAART patients and 5 non-treated HIV and 13 healthy controls.
RESULTSThe levels of CCR5 and CXCR4 on CD4 and CD8 T cells and their CD45RO/CD45RA subsets in HIV-1-infected patients had not any statistical significance than that on control subjects and effective HAART could adjust the expression on T cells.
CONCLUSIONCXCR4/CCR5 plays an important role in the progress of HIV-1 infection. The most favorable condition for treatment should be initiated before stage B.
Acquired Immunodeficiency Syndrome ; drug therapy ; immunology ; Antiretroviral Therapy, Highly Active ; CD4-Positive T-Lymphocytes ; chemistry ; CD8-Positive T-Lymphocytes ; chemistry ; HIV-1 ; Humans ; Receptors, CCR5 ; blood ; drug effects ; Receptors, CXCR4 ; blood ; drug effects
8.Chemical constituents of Alisma orientalis and their immunosuppressive function.
Chaofeng ZHANG ; Aichun ZHOU ; Mian ZHANG
China Journal of Chinese Materia Medica 2009;34(8):994-998
OBJECTIVETo investigate the chemical constituents with immunosuppressive function from Alisma orientalis.
METHODThe chemical constituents were isolated and purified by kinds of column chromatography and its structures were elucidated by NMR spectra and physicochemical properties. Its immunocompentence of lymphocytes taken from spleen of mouse were examined by MTT assay.
RESULTTwelve compounds were isolated and identified as clovandiol (1), orientalol E (2), alismoxide (3), alismol (4), 4alpha, l0alpha-dihydroxy-5beta-H-guaj-6-en (5), alismorientols A (6), alisol F (7), alisol A (8), 13beta,17beta-epoxy alisol A (9), alisol B 23-acetate (10), 1H-indole-3-carboxylic acid (11) and cuccinic acid (12). Compounds 9, 10 and alisol A 24-acetate showed immunosuppressive function.
CONCLUSIONCompounds 1, 5, 11 and 12 were isolated firstly from this genus,and the NMR spectra data of 1 were corrected firstly, some protostan-type triterpenoids may be developed as new drug with immunosuppressive function.
Alisma ; chemistry ; Animals ; Cells, Cultured ; Cholestenones ; chemistry ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Immunosuppressive Agents ; chemistry ; pharmacology ; Indoles ; chemistry ; pharmacology ; Magnetic Resonance Spectroscopy ; Mice ; Mice, Inbred C57BL ; Sesquiterpenes ; chemistry ; pharmacology ; T-Lymphocytes ; cytology ; drug effects ; Triterpenes ; chemistry ; pharmacology
9.Comparative Quantitative Analysis of Cluster of Differentiation 45 Antigen Expression on Lymphocyte Subsets.
Mijeong IM ; Hyojin CHAE ; Taehoon KIM ; Hun Hee PARK ; Jihyang LIM ; Eun Jee OH ; Yonggoo KIM ; Yeon Joon PARK ; Kyungja HAN
The Korean Journal of Laboratory Medicine 2011;31(3):148-153
BACKGROUND: Since the recent introduction of radioimmunotherapy (RIT) using antibodies against cluster of differentiation (CD) 45 for the treatment of lymphoma, the clinical significance of the CD45 antigen has been increasing steadily. Here, we analyzed CD45 expression on lymphocyte subsets using flow cytometry in order to predict the susceptibility of normal lymphocytes to RIT. METHODS: Peripheral blood specimens were collected from 14 healthy individuals aged 25-54 yr. The mean fluorescence intensity (MFI) of the cell surface antigens was measured using a FACSCanto II system (Becton Dickinson Bioscience, USA). MFI values were converted into antibody binding capacity values using a Quantum Simply Cellular microbead kit (Bangs Laboratories, Inc., USA). RESULTS: Among the lymphocyte subsets, the expression of CD45 was the highest (725,368+/-42,763) on natural killer T (NKT) cells, 674,030+/-48,187 on cytotoxic/suppressor T cells, 588,750+/-48,090 on natural killer (NK) cells, 580,211+/-29,168 on helper T (Th) cells, and 499,436+/-21,737 on B cells. The Th cells and NK cells expressed a similar level of CD45 (P=0.502). Forward scatter was the highest in NKT cells (P<0.05), whereas side scatter differed significantly between each of the lymphocyte subsets (P<0.05). CD3 expression was highest in the Th and NKT cells. CONCLUSIONS: NKT cells express the highest levels of CD45 antigen. Therefore, this lymphocyte subset would be most profoundly affected by RIT or pretargeted RIT. The monitoring of this lymphocyte subset during and after RIT should prove helpful.
Adult
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Antibodies/immunology
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Antigens, CD45/*analysis/immunology
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B-Lymphocytes/immunology/metabolism
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CD8-Positive T-Lymphocytes/immunology/metabolism
;
Female
;
Flow Cytometry/*methods
;
Fluorescein-5-isothiocyanate/chemistry
;
Fluorescent Dyes/chemistry
;
Humans
;
Killer Cells, Natural/immunology/metabolism
;
Lymphocytes/immunology/*metabolism
;
Lymphoma/radiotherapy
;
Male
;
Middle Aged
;
Natural Killer T-Cells/immunology/metabolism
;
Protein Binding
;
Radioimmunotherapy
;
Reagent Kits, Diagnostic
;
T-Lymphocytes, Helper-Inducer/immunology/metabolism
10.Comparative Quantitative Analysis of Cluster of Differentiation 45 Antigen Expression on Lymphocyte Subsets.
Mijeong IM ; Hyojin CHAE ; Taehoon KIM ; Hun Hee PARK ; Jihyang LIM ; Eun Jee OH ; Yonggoo KIM ; Yeon Joon PARK ; Kyungja HAN
The Korean Journal of Laboratory Medicine 2011;31(3):148-153
BACKGROUND: Since the recent introduction of radioimmunotherapy (RIT) using antibodies against cluster of differentiation (CD) 45 for the treatment of lymphoma, the clinical significance of the CD45 antigen has been increasing steadily. Here, we analyzed CD45 expression on lymphocyte subsets using flow cytometry in order to predict the susceptibility of normal lymphocytes to RIT. METHODS: Peripheral blood specimens were collected from 14 healthy individuals aged 25-54 yr. The mean fluorescence intensity (MFI) of the cell surface antigens was measured using a FACSCanto II system (Becton Dickinson Bioscience, USA). MFI values were converted into antibody binding capacity values using a Quantum Simply Cellular microbead kit (Bangs Laboratories, Inc., USA). RESULTS: Among the lymphocyte subsets, the expression of CD45 was the highest (725,368+/-42,763) on natural killer T (NKT) cells, 674,030+/-48,187 on cytotoxic/suppressor T cells, 588,750+/-48,090 on natural killer (NK) cells, 580,211+/-29,168 on helper T (Th) cells, and 499,436+/-21,737 on B cells. The Th cells and NK cells expressed a similar level of CD45 (P=0.502). Forward scatter was the highest in NKT cells (P<0.05), whereas side scatter differed significantly between each of the lymphocyte subsets (P<0.05). CD3 expression was highest in the Th and NKT cells. CONCLUSIONS: NKT cells express the highest levels of CD45 antigen. Therefore, this lymphocyte subset would be most profoundly affected by RIT or pretargeted RIT. The monitoring of this lymphocyte subset during and after RIT should prove helpful.
Adult
;
Antibodies/immunology
;
Antigens, CD45/*analysis/immunology
;
B-Lymphocytes/immunology/metabolism
;
CD8-Positive T-Lymphocytes/immunology/metabolism
;
Female
;
Flow Cytometry/*methods
;
Fluorescein-5-isothiocyanate/chemistry
;
Fluorescent Dyes/chemistry
;
Humans
;
Killer Cells, Natural/immunology/metabolism
;
Lymphocytes/immunology/*metabolism
;
Lymphoma/radiotherapy
;
Male
;
Middle Aged
;
Natural Killer T-Cells/immunology/metabolism
;
Protein Binding
;
Radioimmunotherapy
;
Reagent Kits, Diagnostic
;
T-Lymphocytes, Helper-Inducer/immunology/metabolism