1.Costimulatory molecule B7-H1 on the immune escape of bladder cancer and its clinical significance.
Yonghua, WANG ; Qianyuan, ZHUANG ; Siwei, ZHOU ; Zhiquan, HU ; Ruzhu, LAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2009;29(1):77-9
B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were constructed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence (P<0.05). The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.
Antigens, CD/genetics
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Antigens, CD/*metabolism
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Antigens, CD80/genetics
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Antigens, CD80/*metabolism
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Prognosis
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Tumor Escape/*genetics
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Urinary Bladder Neoplasms/*immunology
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Urinary Bladder Neoplasms/metabolism
2.The role of B7 molecules in T cell anergy.
Jing WANG ; Xiaoyan KE ; Liping JIA
Chinese Journal of Hematology 2002;23(7):341-344
OBJECTIVETo explore the role and mechanism of B7 molecules in T cell anergy.
METHODSAnti-B7-1 (CD(80)) and anti-B7-2 (CD(86)) monoclonal antibodies were used to induce T cell anergy. T cell proliferation were assayed by mixed lymphocyte reaction (MLR) with (3)H-TdR incorporation, and cytokine mRNA transcripts were analyzed with reverse transcriptase-polymerase chain reaction (RT-PCR). B7-transfected-CHO cells were used as artificial antigen presentation cells (APCs) in MLR to exclude the effects of other costimulatory molecules.
RESULTSMLR results showed that the proliferation of T cells was inhibited to various extents by anti-CD(80) or anti-CD(86) monoclonal antibody, the effect of anti-CD(86) antibody was greater than that of anti-CD(80) antibody, and the proliferation was totally blocked when the two were used together. The results of RT-PCR demonstrated that IL-2 and IFN-gamma mRNA transcripts decreased whereas IL-4 mRNA transcripts increased in T cell after treatment with anti-B7 antibo-dies for 24 hours. In MLR with artificial APC, signal one (DR7) alone could stimulate T cell proliferation at a certain threshold intensity. Costimulator B7-1 molecule could help signal one in T cell proliferation. This effect was blocked by anti-CD(80).
CONCLUSIONB7 molecules play an important role in T cell immune response. Blockade of B7 family resulted in T cell anergy. The role of CD(86) may be more important than that of CD(80). The conversion of cytokine profile from Th1's to Th2's reflected that anergetic T cells were differentiated into Th2 cells by anti-B7 suggesting that anergetic blockade of costimulator molecules may be one of the mechanisms of T cell.
Animals ; Antigens, CD ; genetics ; B7 Antigens ; B7-1 Antigen ; metabolism ; Cricetulus ; Lymphocyte Activation ; immunology ; Membrane Glycoproteins ; T-Lymphocytes ; immunology
3.Hot issues of immunology in viral hepatitis C.
Chinese Journal of Hepatology 2009;17(7):490-493
Animals
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Antigens, CD
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immunology
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Cytokines
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metabolism
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Hepacivirus
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immunology
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Hepatitis C
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immunology
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prevention & control
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virology
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Hepatitis C Antibodies
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biosynthesis
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immunology
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Hepatitis C Antigens
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immunology
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Humans
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Killer Cells, Natural
;
immunology
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T-Lymphocytes
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immunology
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metabolism
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T-Lymphocytes, Regulatory
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immunology
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metabolism
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Viral Proteins
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immunology
4.Regulatory T cells and asthma.
Sheng-Tao ZHAO ; Chang-Zheng WANG
Journal of Zhejiang University. Science. B 2018;19(9):663-673
Asthma is a chronic disease of airway inflammation due to excessive T helper cell type 2 (Th2) response. Present treatment based on inhalation of synthetic glucocorticoids can only control Th2-driven chronic eosinophilic inflammation, but cannot change the immune tolerance of the body to external allergens. Regulatory T cells (Tregs) are the main negative regulatory cells of the immune response. Tregs play a great role in regulating allergic, autoimmune, graft-versus-host responses, and other immune responses. In this review, we will discuss the classification and biological characteristics, the established immunomodulatory mechanisms, and the characteristics of induced differentiation of Tregs. We will also discuss the progress of Tregs in the field of asthma. We believe that further studies on the regulatory mechanisms of Tregs will provide better treatments and control strategies for asthma.
Antigens, CD/analysis*
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Apyrase/analysis*
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Asthma/immunology*
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Cell Differentiation
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Cytokines/metabolism*
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Humans
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Lymphocyte Transfusion
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T-Lymphocytes, Regulatory/immunology*
5.Overexpression of pulmonary surfactant protein A like molecules in inflammatory bowel disease tissues.
Jun-ming LUO ; Zhao-qian LIU ; Chin Y EUGENE
Journal of Central South University(Medical Sciences) 2008;33(11):979-986
OBJECTIVE:
To investigate the distribution of pulmonary surfactant protein A (SP-A) like molecules and the bridge of frontier host defense and adaptive immune response cell of CD68 positive macrophages in inflammatory bowel disease (IBD).
METHODS:
Surgical specimens derived from involved areas and normal area of the colon with Crohn disease (CD) and ulcerative colitis (UC) were obtained from Department of Pathology, Rhode Island Hospital, Brown University Medical Center. The distribution of SP-A like molecule in intestine of IBD was detected by immunohistochemistry.
RESULTS:
SP-A like molecule located in epithelia of intestine, the surface of intestine villi, blood vessels of connective tissue, and some inflammatory cells. The number of macrophages with both SP-A like molecule and CD68 positive was dramatically increased in the inflammatory area than the normal area. Some CD68 positive macrophages expressed SP-A like immunoreactivity by immunofluorescence double labeling.
CONCLUSION
SP-A is an important host defense molecule in lung, and SP-A expression in large intestine may reflect a close relation between 2 organs in immune response towards inflammation.
Antigens, CD
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metabolism
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Antigens, Differentiation, Myelomonocytic
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metabolism
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Colitis, Ulcerative
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immunology
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metabolism
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Colon
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metabolism
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Crohn Disease
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immunology
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metabolism
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Humans
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Immunohistochemistry
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Inflammatory Bowel Diseases
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immunology
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metabolism
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Macrophages
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immunology
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metabolism
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Pulmonary Surfactant-Associated Proteins
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genetics
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metabolism
6.Immunophenotypic Analysis of Acute Promyelocytic Leukemia.
Fang CHEN ; Yan-Ping HU ; Xiao-Hui WANG ; Shuang FU ; Yu FU ; Xuan LIU ; Min-Yu ZHANG ; Shao-Kun WANG ; Ji-Hong ZHANG
Journal of Experimental Hematology 2016;24(2):321-325
OBJECTIVETo investigate the immunophenotype of leukemia promyelocytes (LP) in bone marrow of patients with acute promyelocytic leukemia (APL) and to explore their characteristics and significance.
METHODSThe immunophenotypes of leukemia cells in 43 patients with APL were analyzed by means of 4 color immunophenotypes; the cell population in which CD45 strength localized at 10(2) and the SSC strength locatized at 10(2) was defined as R3, the cell population in which CD45 strength localized at 10(3) and the SSC strength localized at 10(2) was defined as R5, moreover the ratio of positive cells >80% was defined as strong positive expression, the ratio of positive cells between 20%-80% was difined as weak positive expression, the ratio of positive cells <20% was difined as negative by gating method of CD45/SSC.
RESULTSThere was a abnormal cell population (R3) in 79.07% cases; the immunophenotypes of R3 was cheracteried by high SSC, weaker expression of CD45, the rate of CD38, CD9 and CD13 all was 100%, moreover their bright expression (>80%) was 86.05%, 90.70% and 86.05%, respectively; the positive expression rate of CD33, CD117 and CD64 was 97.67%, 95.35% and 83.80% respectively, moreover thier bright expression was 84.04%, 69.77% and 30.23% respectively; the CD15 was weakly expressed in 39.53% cases, the CD34 and HLA-DR were weakly expression in 16.28% and 6.98% cases respectively. All the cases did not express CD116. There were 2 cell populations (R3 and R5) in 20.93% cases, the immunophenotypic features of R3 were cosistant with above mentioning, while the immunophenotypes of R5 were lower than those of R3 SSC; the fluorescence intensity of CD45 was higher, but lower than that in normal lymphycytes, the positive rate of CD9, CD13, MPO was 100%, moreover thier fluorescence intensity was high; they did not expressed CD123, CD25, CD22, CD4, CD64 and CD14. Thereby it can be concluded that the typical immunophenotypes is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-) in APL. There was a special immunophenotype in the APL with basophilic granules. Conclusoin: APL has a characteristic immunophenotypic profile, whose typical immunophenotype is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-). The special immunophenotype exists in the APL with basophilic granules. Flow cytometric immunophenotyping may be a useful for rapid recognition of APL and has significant for prognosis.
Antigens, CD ; metabolism ; Cell Count ; Flow Cytometry ; Granulocyte Precursor Cells ; classification ; HLA-DR Antigens ; metabolism ; Humans ; Immunophenotyping ; Leukemia, Promyelocytic, Acute ; classification ; immunology ; Leukocyte Common Antigens ; metabolism ; Prognosis
7.CD99 activates T cells via a costimulatory function that promotes raft association of TCR complex and tyrosine phosphorylation of TCR zeta.
Kwon Ik OH ; Byoung Kwon KIM ; Young Larn BAN ; Eun Young CHOI ; Kyeong Cheon JUNG ; Im Soon LEE ; Seong Hoe PARK
Experimental & Molecular Medicine 2007;39(2):176-184
We investigated the co-stimulatory role of a cell-surface protein, CD99. Co-ligation of CD99 and suboptimal CD3 induced T-cell activation to a level comparable to that obtained with optimal CD3 or CD3+CD28. We also noted concomitant enhancement of the earliest T-cell receptor (TCR) signaling events. In addition, co-ligation of CD99 and CD3 led to translocation of TCR complexes into the lipid raft, without concomitant migration of CD99 to the raft, and consequent enhancement of TCR zeta-mediated signal 1. These data demonstrate the unique properties of CD99 co-stimulation that distinguish this molecule from CD28 and other raft-resident co-stimulatory factors.
Antigens, CD/*immunology
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Antigens, CD3/immunology
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Cell Adhesion Molecules/*immunology
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Down-Regulation
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Humans
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Jurkat Cells
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Lymphocyte Activation/*immunology
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Membrane Microdomains/*immunology
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Membrane Proteins/*immunology
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Phosphorylation
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Phosphotyrosine/*metabolism
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Protein Transport
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Receptors, Antigen, T-Cell/*immunology
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T-Lymphocytes/*immunology
8.Immunoreactivity of CD99 in Non-Hodgkin's Lymphoma: Unexpected Frequent Expression in ALK-positive Anaplastic Large Cell Lymphoma.
Chang Ohk SUNG ; Young H KO ; Sanghui PARK ; Kihyun KIM ; Wonseog KIM
Journal of Korean Medical Science 2005;20(6):952-956
To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.
Antigens, CD/*metabolism
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Blotting, Western
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Cell Adhesion Molecules/*metabolism
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Humans
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Immunohistochemistry
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Lymphoma, Large-Cell/enzymology/*immunology/pathology
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Lymphoma, Non-Hodgkin/enzymology/*immunology/pathology
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Protein-Tyrosine Kinase/immunology/*metabolism
10.Role of CD28/CTLA-4 co-stimulators in immune pathophysiology of aplastic anemia.
Guang-Sheng HE ; Ling ZHOU ; De-Pei WU ; Ai-Ning SUN ; Miao MIAO ; Xiu-Li WANG ; Wei-Rong CHANG ; Zi-Ling ZHU ; Zheng-Ming JIN ; Hui-Ying QIU ; Xiao-Wen TANG ; Zheng-Zheng FU ; Yue HAN ; Xiao MA ; Su-Ning CHEN ; Xiao-Jin WU
Chinese Journal of Hematology 2007;28(9):590-593
OBJECTIVETo explore the possible role of CD28/CTLA-4 co-stimulators in immune pathophysiology of acquired aplastic anemia(AA).
METHODSBy FACS, the percentages of CD28, CTLA-4 expressing CD3+ CD4+ T cells and the level of Th1, Th2 in bone marrow were detected in 23 AA patients at active phase, 10 at recovery phase and 15 normal controls. The relationship between the co-stimulators, Th1, Th2, and absolute neutrophil counts (ANC) was evaluated.
RESULTS(1) The percentage of CD28 and CTLA-4 expressing CD3+ CD4+ T cells in bone marrow, and CD28+/CTLA-4+ ratios were (31.40 +/- 10.83)%, (2.45 +/- 1.30)% , and 17.02 +/- 13.44 in normal controls respectively, (39.84 +/- 10.89)%, (1.43 +/- 0.67)%, and 43.04 +/- 37.61 in AA at active phase, respectively, (22 +/- 9.08)%, (3.46 +/- 2.26)%, and 10.49 +/- 7.8 in AA at recovery phase, respectively. The percentage of CD28 and CD28+/CTLA-4+ ratio were significantly higher, while CTLA-4 were lower in active phase AA patients than in normal controls (P < 0.05). These values in recovery phase AA were comparable to those in normal controls. (The Th1, Th2, and Th1/Th2 in bone marrow were (4.21 +/- 2.11)%, (1.99 +/- 1.27)%, and 2.46 +/- 1.28 in normal controls respectively, (11.13 +/- 4. 96)%, (2.46 +/- 1.65)%, and 5.20 +/- 1.98 in active phase AA and (5.39 +/- 4.2)9%, (2.53 +/- 2.41)%, and 2.87 +/- 1.43 in recovery phase AA, respectively. The percentage of Th1 and Th1/Th2 ratio were significantly higher in AA patients at active phase than in normal controls (P < 0.05). (3) The CD28+/CTLA-4+ ratio was positively related to the Th1+ /Th2+ ratio (P < 0.05). ANC was negatively related to CD3+ CD4+ CD28+ T cells (P < 0.01), and positively to CD3 + CD4 ' CTLA-4' T cells (P < 0.01) respectively.
CONCLUSION(1) The expression of CD28 was increased while CTLA-4 decreased on the membranes of CD3+ CD4+ T cells in bone marrow of AA patients. (2) The abnormal expression of CD28 costimulator promoted the shift of immune balance to Thl type. (3) The unbalance of CD28+ / CTLA-4+ is important for the immune pathophysiology of AA.
Adolescent ; Adult ; Aged ; Anemia, Aplastic ; immunology ; metabolism ; Antigens, CD ; immunology ; metabolism ; CD28 Antigens ; immunology ; metabolism ; CD4-Positive T-Lymphocytes ; metabolism ; CTLA-4 Antigen ; Child ; Female ; Humans ; Male ; Middle Aged ; Th1 Cells ; immunology ; Th2 Cells ; immunology