Multiple negative feedbacks on CD152 expression in allograft tolerance

Meng-Kun Tsai; Hong-Nerng Ho; Hsiung-Fei Chien; Mei-Ching Tzeng; Chien-Hsing Chen; Po-Huang Lee

doi:10.1097/01.TP.0000146428.03625.EB

Multiple negative feedbacks on CD152 expression in allograft tolerance

Meng-Kun Tsai, Hong-Nerng Ho, Hsiung-Fei Chien, Mei-Ching Tzeng, Chien-Hsing Chen, Po-Huang Lee

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Background. CD152 has been implicated in tolerance induction. This study investigated how CD80 and CD86 regulated CD152 expression in a low-responding cardiac transplant model with CD152-mediated long-term graft acceptance. Methods. A low-responding cardiac transplant model from BALB/c to B10.A was used. Donor-specific stimulation and multiple antibody blockade of the CD80/CD86:CD28/CD152 co-stimulatory pathway was applied to the splenic T cells from B10.A recipients with 100-day grafts (B10.A-100). Proliferation assays, quantitative (Q) real-time polymerase chain reaction (PCR), flow cytometric analyses, and fluorescence microscopy were conducted to examine the roles of CD80 and CD86 in CD152 expression. Results. B10.A-100 splenic T cells were hyporesponsive to donor-specific stimulation, and anti-CD80, anti-CD86, or anti-CD152 treatment significantly enhanced the proliferation response of the B10.A-100 splenic T cells. Proliferation assays and Q-PCR revealed that CD152 inhibited T-cell proliferation and, at the same time, decreased CD152 expression by secluding CD80 and CD86 from CD28 engagement. Flow cytometric analyses and fluorescence microscopy showed that CD28 engagement facilitated intracellular accumulation of CD152. Besides, CD152 engagement by CD80 decreased CD152 mRNA transcription, and CD152 engagement by CD86 inhibited surface expression of CD152. Conclusions. CD80 and CD86 controlled CD152-mediated allograft tolerance by multiple negative feedbacks on CD152 mRNA and surface expression.

Original language	English
Pages (from-to)	174-181
Number of pages	8
Journal	Transplantation
Volume	79
Issue number	2
DOIs	https://doi.org/10.1097/01.TP.0000146428.03625.EB
Publication status	Published - 2005
Externally published	Yes

Keywords

CD152
CD80
CD86
Transplant tolerance
B7 antigen
B7 monoclonal antibody
CD86 antigen
cytotoxic T lymphocyte antigen 4
lymphocyte antigen
messenger RNA
monoclonal antibody
monoclonal antibody cd152
monoclonal antibody CD28
monoclonal antibody CD80
monoclonal antibody cd86
unclassified drug
animal cell
animal experiment
antigen expression
article
controlled study
female
flow cytometry
fluorescence microscopy
heart graft
heart transplantation
lymphocyte proliferation
mouse
mouse strain
negative feedback
nonhuman
organ donor
priority journal
real time polymerase chain reaction
recipient
RNA transcription
spleen cell
T lymphocyte
transplantation tolerance
Animals
Antigens, CD
Antigens, CD80
Antigens, CD86
Antigens, Differentiation
Cell Division
DNA Primers
Female
Heart Transplantation
Immune Tolerance
Lymphocyte Activation
Membrane Glycoproteins
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Spleen
T-Lymphocytes
Transcription, Genetic
Transplantation, Homologous

Access to Document

10.1097/01.TP.0000146428.03625.EB

http://www.scopus.com/inward/record.url?eid=2-s2.0-12744260038&partnerID=40&md5=a4c08a28f94941bc198bf84877bfa1e6

Cite this

@article{e962c1b322cc4cf285b856d6222f350f,

title = "Multiple negative feedbacks on CD152 expression in allograft tolerance",

abstract = "Background. CD152 has been implicated in tolerance induction. This study investigated how CD80 and CD86 regulated CD152 expression in a low-responding cardiac transplant model with CD152-mediated long-term graft acceptance. Methods. A low-responding cardiac transplant model from BALB/c to B10.A was used. Donor-specific stimulation and multiple antibody blockade of the CD80/CD86:CD28/CD152 co-stimulatory pathway was applied to the splenic T cells from B10.A recipients with 100-day grafts (B10.A-100). Proliferation assays, quantitative (Q) real-time polymerase chain reaction (PCR), flow cytometric analyses, and fluorescence microscopy were conducted to examine the roles of CD80 and CD86 in CD152 expression. Results. B10.A-100 splenic T cells were hyporesponsive to donor-specific stimulation, and anti-CD80, anti-CD86, or anti-CD152 treatment significantly enhanced the proliferation response of the B10.A-100 splenic T cells. Proliferation assays and Q-PCR revealed that CD152 inhibited T-cell proliferation and, at the same time, decreased CD152 expression by secluding CD80 and CD86 from CD28 engagement. Flow cytometric analyses and fluorescence microscopy showed that CD28 engagement facilitated intracellular accumulation of CD152. Besides, CD152 engagement by CD80 decreased CD152 mRNA transcription, and CD152 engagement by CD86 inhibited surface expression of CD152. Conclusions. CD80 and CD86 controlled CD152-mediated allograft tolerance by multiple negative feedbacks on CD152 mRNA and surface expression.",

keywords = "CD152, CD80, CD86, Transplant tolerance, B7 antigen, B7 monoclonal antibody, CD86 antigen, cytotoxic T lymphocyte antigen 4, lymphocyte antigen, messenger RNA, monoclonal antibody, monoclonal antibody cd152, monoclonal antibody CD28, monoclonal antibody CD80, monoclonal antibody cd86, unclassified drug, animal cell, animal experiment, antigen expression, article, controlled study, female, flow cytometry, fluorescence microscopy, heart graft, heart transplantation, lymphocyte proliferation, mouse, mouse strain, negative feedback, nonhuman, organ donor, priority journal, real time polymerase chain reaction, recipient, RNA transcription, spleen cell, T lymphocyte, transplantation tolerance, Animals, Antigens, CD, Antigens, CD80, Antigens, CD86, Antigens, Differentiation, Cell Division, DNA Primers, Female, Heart Transplantation, Immune Tolerance, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Spleen, T-Lymphocytes, Transcription, Genetic, Transplantation, Homologous",

author = "Meng-Kun Tsai and Hong-Nerng Ho and Hsiung-Fei Chien and Mei-Ching Tzeng and Chien-Hsing Chen and Po-Huang Lee",

note = "被引用次數：1 Export Date: 16 March 2016 CODEN: TRPLA 通訊地址: Lee, P.-H.; Department of Surgery, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan; 電子郵件： [email protected] 化學物質/CAS: Antigens, CD; Antigens, CD80; Antigens, CD86; Antigens, Differentiation; Cd86 protein, mouse; cytotoxic T-lymphocyte antigen 4; DNA Primers; Membrane Glycoproteins 製造商： Pharmingen, United States 參考文獻: Tivol, E., Borriello, F., Schweitzer, A., Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan destruction, revealing a critical negative regulatory role of CTLA-4 (1995) Immunity, 3, pp. 541-547; Waterhouse, P., Penninger, J., Timms, E., Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4 (1995) Science, 270, pp. 985-988; Carreno, B.M., Bennett, F., Chau, T.A., CTLA-4 (CD152) can inhibit T cell activation by two different mechanisms depending on its level of cell surface expression (2000) J Immunol, 165, pp. 1352-1356; Lee, K.M., Chuang, E., Griffin, M., Molecular basis of T cell inactivation by CTLA-4 (1998) Science, 282, pp. 2263-2266; Calvo, C.R., Amsen, D., Kruisbeek, A.M., Cytotoxic T lymphocyte antigen 4 (CTLA-4) interferes with extracellular NH2-terminal kinase (JNK) activation, but does not affect phosphorylation of T cell receptor zeta and ZAP70 (1997) J Exp Med, 186, pp. 1645-1653; Alegre, M.L., Noel, P.J., Eisfelder, B.J., Regulation of surface and intracellular expression of CTLA4 on mouse T cells (1996) J Immunol, 157, pp. 4762-4770; Walunas, T.L., Bakker, C.Y., Bluestone, J.A., CTLA-4 ligation blocks CD28-dependent T cell activation (1996) J Exp Med, 183, pp. 2541-2550; Dahlen, E., Hedlund, G., Dawe, K., Low CD86 expression in the nonobese diabetic mouse results in the impairment of both T cell activation and CTLA-4 up-regulation (2000) J Immunol, 164, pp. 2444-2456; Salomon, B., Lenschow, D.J., Rhee, L., B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes (2000) Immunity, 12, pp. 431-440; Salomon, B., Bluestone, J.A., Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation (2001) Annu Rev Immunol, 19, pp. 225-252; Judge, T.A., Wu, Z., Zheng, X.G., The role of CD80, CD86, and CTLA-4 in alloimmune responses and the induction of long-term allograft survival (1999) J Immunol, 162, pp. 1947-1951; Chai, J.G., Vendetti, S., Amofah, E., CD152 ligation by CD80 on T cells is required for the induction of unresponsiveness by costimulation-deficient antigen presentation (2000) J Immunol, 165, pp. 3037-3042; Bour-Jordan, H., Bluestone, J.A., CD28 function: A balance of costimulatory and regulatory signals (2002) J Clin Immunol, 22, pp. 1-7; Collins, A.V., Brodie, D.W., Gilbert, R.J.C., The interaction properties of costimulatory molecules revisited (2002) Immunity, 17, pp. 201-210; Tsai, M.K., Ho, H.N., Chien, H.F., The role of B7 ligands (CD80 and CD86) in CD 152-mediated allograft tolerance: A crosscheck hypothesis (2004) Transplantation, 77, pp. 48-54; Chen, Z., A technique of cervical heterotopic heart transplantation in mice (1991) Transplantation, 52, p. 1099; Kaithamana, S., Fan, J., Osuga, Y., Induction of experimental autoimmune Graves' disease in BALB/c mice (1999) J Immunol, 163, pp. 5157-5164; Tsai, M.K., Lin, R.H., Hsu, B.R., Lipofection of pcDNA3-CTLA4-Ig into B cells promotes allogeneic hyporesponsiveness (2003) Transplant Proc, 35, pp. 548-549; Ling, V., Wu, P.W., Finnerty, H.F., Complete sequence determination of the mouse and human CTLA4 gene loci: Cross-species DNA sequence similarity beyond exon borders (1999) Genomics, 60, pp. 341-355; Sheu, B.C., Lin, R.H., Ho, H.N., Down-regulation of CD25 expression on the surface of activated tumor-infiltrating lymphocytes in human cervical carcinoma (1997) Hum Immunol, 56, pp. 39-48; Wang, S.M., Hwang, R.D., Greenberg, A.S., Temporal and spatial assembly of lipid droplet-associated proteins in 3T3-L1 preadipocytes (2003) Histochem Cell Biol, 120, pp. 285-292; Roncarolo, M.G., Gregori, S., Levings, M., Type 1 T regulatory cells and their relationship with CD4+CD25+ T regulatory cells (2003) Novartis Found Symp, 252, pp. 115-131; Egen, J.G., Allison, J.P., Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength (2002) Immunity, 16, pp. 23-35; Baroja, M.L., Vijayakrishnan, L., Bettelli, E., Inhibition of CTLA-4 function by the regulatory subunit of serine/threonine phosphatase 2A (2002) J Immunol, 168, pp. 5070-5078; Chuang, E., Alegre, M.L., Duckett, C.S., Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression (1997) J Immunol, 159, pp. 144-151; Sansom, D.M., Manzotti, C.N., Zheng, Y., What's the difference between CD80 and CD86 (2003) Trends Immunol, 24, pp. 313-317; Zheng, Y., Manzotti, C.N., Liu, M., CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells (2004) J Immunol, 172, pp. 2778-2784; Lohr, J., Knoechel, B., Jiang, S., The inhibitory function of B7 costimulatiors in T cell responses to foreign and self-antigens (2003) Nat Immunol, 4, pp. 664-669; Boise, L.H., Minn, A.J., Noel, P.J., CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL (1995) Immunity, 3, pp. 87-98; Viola, A., Lanzavecchia, A., T cell activation determined by T cell receptor number and tunable thresholds (1996) Science, 273, pp. 104-106; Iida, T., Ohno, H., Nakaseko, C., Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4+ T cells (2000) J Immumol, 165, pp. 5062-5068; Russell, P.S., Chase, C.M., Colvin, R.B., Alloantibody- and T cell-mediated immunity in the pathogenesis of transplant arteriosclerosis (1997) Transplantation, 64, p. 1531; Sprent, J., Schaefer, M., Lo, D., Properties of purified T cell subsets: II. In vivo response to class I vs class II H-2 differences (1986) J Exp Med, 165, p. 1296; Tsai, M.K., Ho, H.N., Chien, H.F., Visualization of the CD4+CD25+CTLA-4+ T-cell subset in long-term surviving cardiac allografts (2002) Transplantation, 74 (SUPPL.), p. 592; Ariyan, C., Salvalaggio, P., Fecteau, S., Cutting edge: Transplantation tolerance through enhanced CTLA-4 expression (2003) J Immunol, 171, pp. 5673-5677; Hori, S., Nomura, T., Sakaguchi, S., Control of regulatory T cell development by the transcription factor Foxp3 (2003) Science, 299, pp. 1057-1061",

year = "2005",

doi = "10.1097/01.TP.0000146428.03625.EB",

language = "English",

volume = "79",

pages = "174--181",

journal = "Transplantation",

issn = "0041-1337",

publisher = "Lippincott Williams and Wilkins",

number = "2",

}

TY - JOUR

T1 - Multiple negative feedbacks on CD152 expression in allograft tolerance

AU - Tsai, Meng-Kun

AU - Ho, Hong-Nerng

AU - Chien, Hsiung-Fei

AU - Tzeng, Mei-Ching

AU - Chen, Chien-Hsing

AU - Lee, Po-Huang

N1 - 被引用次數：1 Export Date: 16 March 2016 CODEN: TRPLA 通訊地址: Lee, P.-H.; Department of Surgery, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan; 電子郵件： [email protected] 化學物質/CAS: Antigens, CD; Antigens, CD80; Antigens, CD86; Antigens, Differentiation; Cd86 protein, mouse; cytotoxic T-lymphocyte antigen 4; DNA Primers; Membrane Glycoproteins 製造商： Pharmingen, United States 參考文獻: Tivol, E., Borriello, F., Schweitzer, A., Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan destruction, revealing a critical negative regulatory role of CTLA-4 (1995) Immunity, 3, pp. 541-547; Waterhouse, P., Penninger, J., Timms, E., Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4 (1995) Science, 270, pp. 985-988; Carreno, B.M., Bennett, F., Chau, T.A., CTLA-4 (CD152) can inhibit T cell activation by two different mechanisms depending on its level of cell surface expression (2000) J Immunol, 165, pp. 1352-1356; Lee, K.M., Chuang, E., Griffin, M., Molecular basis of T cell inactivation by CTLA-4 (1998) Science, 282, pp. 2263-2266; Calvo, C.R., Amsen, D., Kruisbeek, A.M., Cytotoxic T lymphocyte antigen 4 (CTLA-4) interferes with extracellular NH2-terminal kinase (JNK) activation, but does not affect phosphorylation of T cell receptor zeta and ZAP70 (1997) J Exp Med, 186, pp. 1645-1653; Alegre, M.L., Noel, P.J., Eisfelder, B.J., Regulation of surface and intracellular expression of CTLA4 on mouse T cells (1996) J Immunol, 157, pp. 4762-4770; Walunas, T.L., Bakker, C.Y., Bluestone, J.A., CTLA-4 ligation blocks CD28-dependent T cell activation (1996) J Exp Med, 183, pp. 2541-2550; Dahlen, E., Hedlund, G., Dawe, K., Low CD86 expression in the nonobese diabetic mouse results in the impairment of both T cell activation and CTLA-4 up-regulation (2000) J Immunol, 164, pp. 2444-2456; Salomon, B., Lenschow, D.J., Rhee, L., B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes (2000) Immunity, 12, pp. 431-440; Salomon, B., Bluestone, J.A., Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation (2001) Annu Rev Immunol, 19, pp. 225-252; Judge, T.A., Wu, Z., Zheng, X.G., The role of CD80, CD86, and CTLA-4 in alloimmune responses and the induction of long-term allograft survival (1999) J Immunol, 162, pp. 1947-1951; Chai, J.G., Vendetti, S., Amofah, E., CD152 ligation by CD80 on T cells is required for the induction of unresponsiveness by costimulation-deficient antigen presentation (2000) J Immunol, 165, pp. 3037-3042; Bour-Jordan, H., Bluestone, J.A., CD28 function: A balance of costimulatory and regulatory signals (2002) J Clin Immunol, 22, pp. 1-7; Collins, A.V., Brodie, D.W., Gilbert, R.J.C., The interaction properties of costimulatory molecules revisited (2002) Immunity, 17, pp. 201-210; Tsai, M.K., Ho, H.N., Chien, H.F., The role of B7 ligands (CD80 and CD86) in CD 152-mediated allograft tolerance: A crosscheck hypothesis (2004) Transplantation, 77, pp. 48-54; Chen, Z., A technique of cervical heterotopic heart transplantation in mice (1991) Transplantation, 52, p. 1099; Kaithamana, S., Fan, J., Osuga, Y., Induction of experimental autoimmune Graves' disease in BALB/c mice (1999) J Immunol, 163, pp. 5157-5164; Tsai, M.K., Lin, R.H., Hsu, B.R., Lipofection of pcDNA3-CTLA4-Ig into B cells promotes allogeneic hyporesponsiveness (2003) Transplant Proc, 35, pp. 548-549; Ling, V., Wu, P.W., Finnerty, H.F., Complete sequence determination of the mouse and human CTLA4 gene loci: Cross-species DNA sequence similarity beyond exon borders (1999) Genomics, 60, pp. 341-355; Sheu, B.C., Lin, R.H., Ho, H.N., Down-regulation of CD25 expression on the surface of activated tumor-infiltrating lymphocytes in human cervical carcinoma (1997) Hum Immunol, 56, pp. 39-48; Wang, S.M., Hwang, R.D., Greenberg, A.S., Temporal and spatial assembly of lipid droplet-associated proteins in 3T3-L1 preadipocytes (2003) Histochem Cell Biol, 120, pp. 285-292; Roncarolo, M.G., Gregori, S., Levings, M., Type 1 T regulatory cells and their relationship with CD4+CD25+ T regulatory cells (2003) Novartis Found Symp, 252, pp. 115-131; Egen, J.G., Allison, J.P., Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength (2002) Immunity, 16, pp. 23-35; Baroja, M.L., Vijayakrishnan, L., Bettelli, E., Inhibition of CTLA-4 function by the regulatory subunit of serine/threonine phosphatase 2A (2002) J Immunol, 168, pp. 5070-5078; Chuang, E., Alegre, M.L., Duckett, C.S., Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression (1997) J Immunol, 159, pp. 144-151; Sansom, D.M., Manzotti, C.N., Zheng, Y., What's the difference between CD80 and CD86 (2003) Trends Immunol, 24, pp. 313-317; Zheng, Y., Manzotti, C.N., Liu, M., CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells (2004) J Immunol, 172, pp. 2778-2784; Lohr, J., Knoechel, B., Jiang, S., The inhibitory function of B7 costimulatiors in T cell responses to foreign and self-antigens (2003) Nat Immunol, 4, pp. 664-669; Boise, L.H., Minn, A.J., Noel, P.J., CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL (1995) Immunity, 3, pp. 87-98; Viola, A., Lanzavecchia, A., T cell activation determined by T cell receptor number and tunable thresholds (1996) Science, 273, pp. 104-106; Iida, T., Ohno, H., Nakaseko, C., Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4+ T cells (2000) J Immumol, 165, pp. 5062-5068; Russell, P.S., Chase, C.M., Colvin, R.B., Alloantibody- and T cell-mediated immunity in the pathogenesis of transplant arteriosclerosis (1997) Transplantation, 64, p. 1531; Sprent, J., Schaefer, M., Lo, D., Properties of purified T cell subsets: II. In vivo response to class I vs class II H-2 differences (1986) J Exp Med, 165, p. 1296; Tsai, M.K., Ho, H.N., Chien, H.F., Visualization of the CD4+CD25+CTLA-4+ T-cell subset in long-term surviving cardiac allografts (2002) Transplantation, 74 (SUPPL.), p. 592; Ariyan, C., Salvalaggio, P., Fecteau, S., Cutting edge: Transplantation tolerance through enhanced CTLA-4 expression (2003) J Immunol, 171, pp. 5673-5677; Hori, S., Nomura, T., Sakaguchi, S., Control of regulatory T cell development by the transcription factor Foxp3 (2003) Science, 299, pp. 1057-1061

PY - 2005

Y1 - 2005

N2 - Background. CD152 has been implicated in tolerance induction. This study investigated how CD80 and CD86 regulated CD152 expression in a low-responding cardiac transplant model with CD152-mediated long-term graft acceptance. Methods. A low-responding cardiac transplant model from BALB/c to B10.A was used. Donor-specific stimulation and multiple antibody blockade of the CD80/CD86:CD28/CD152 co-stimulatory pathway was applied to the splenic T cells from B10.A recipients with 100-day grafts (B10.A-100). Proliferation assays, quantitative (Q) real-time polymerase chain reaction (PCR), flow cytometric analyses, and fluorescence microscopy were conducted to examine the roles of CD80 and CD86 in CD152 expression. Results. B10.A-100 splenic T cells were hyporesponsive to donor-specific stimulation, and anti-CD80, anti-CD86, or anti-CD152 treatment significantly enhanced the proliferation response of the B10.A-100 splenic T cells. Proliferation assays and Q-PCR revealed that CD152 inhibited T-cell proliferation and, at the same time, decreased CD152 expression by secluding CD80 and CD86 from CD28 engagement. Flow cytometric analyses and fluorescence microscopy showed that CD28 engagement facilitated intracellular accumulation of CD152. Besides, CD152 engagement by CD80 decreased CD152 mRNA transcription, and CD152 engagement by CD86 inhibited surface expression of CD152. Conclusions. CD80 and CD86 controlled CD152-mediated allograft tolerance by multiple negative feedbacks on CD152 mRNA and surface expression.

AB - Background. CD152 has been implicated in tolerance induction. This study investigated how CD80 and CD86 regulated CD152 expression in a low-responding cardiac transplant model with CD152-mediated long-term graft acceptance. Methods. A low-responding cardiac transplant model from BALB/c to B10.A was used. Donor-specific stimulation and multiple antibody blockade of the CD80/CD86:CD28/CD152 co-stimulatory pathway was applied to the splenic T cells from B10.A recipients with 100-day grafts (B10.A-100). Proliferation assays, quantitative (Q) real-time polymerase chain reaction (PCR), flow cytometric analyses, and fluorescence microscopy were conducted to examine the roles of CD80 and CD86 in CD152 expression. Results. B10.A-100 splenic T cells were hyporesponsive to donor-specific stimulation, and anti-CD80, anti-CD86, or anti-CD152 treatment significantly enhanced the proliferation response of the B10.A-100 splenic T cells. Proliferation assays and Q-PCR revealed that CD152 inhibited T-cell proliferation and, at the same time, decreased CD152 expression by secluding CD80 and CD86 from CD28 engagement. Flow cytometric analyses and fluorescence microscopy showed that CD28 engagement facilitated intracellular accumulation of CD152. Besides, CD152 engagement by CD80 decreased CD152 mRNA transcription, and CD152 engagement by CD86 inhibited surface expression of CD152. Conclusions. CD80 and CD86 controlled CD152-mediated allograft tolerance by multiple negative feedbacks on CD152 mRNA and surface expression.

KW - CD152

KW - CD80

KW - CD86

KW - Transplant tolerance

KW - B7 antigen

KW - B7 monoclonal antibody

KW - CD86 antigen

KW - cytotoxic T lymphocyte antigen 4

KW - lymphocyte antigen

KW - messenger RNA

KW - monoclonal antibody

KW - monoclonal antibody cd152

KW - monoclonal antibody CD28

KW - monoclonal antibody CD80

KW - monoclonal antibody cd86

KW - unclassified drug

KW - animal cell

KW - animal experiment

KW - antigen expression

KW - article

KW - controlled study

KW - female

KW - flow cytometry

KW - fluorescence microscopy

KW - heart graft

KW - heart transplantation

KW - lymphocyte proliferation

KW - mouse

KW - mouse strain

KW - negative feedback

KW - nonhuman

KW - organ donor

KW - priority journal

KW - real time polymerase chain reaction

KW - recipient

KW - RNA transcription

KW - spleen cell

KW - T lymphocyte

KW - transplantation tolerance

KW - Animals

KW - Antigens, CD

KW - Antigens, CD80

KW - Antigens, CD86

KW - Antigens, Differentiation

KW - Cell Division

KW - DNA Primers

KW - Female

KW - Heart Transplantation

KW - Immune Tolerance

KW - Lymphocyte Activation

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Polymerase Chain Reaction

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Spleen

KW - T-Lymphocytes

KW - Transcription, Genetic

KW - Transplantation, Homologous

U2 - 10.1097/01.TP.0000146428.03625.EB

DO - 10.1097/01.TP.0000146428.03625.EB

M3 - Article

SN - 0041-1337

VL - 79

SP - 174

EP - 181

JO - Transplantation

JF - Transplantation

IS - 2

ER -

Multiple negative feedbacks on CD152 expression in allograft tolerance

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Keywords

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