The role of B7 ligands (CD80 and CD86) in CD152-mediated allograft tolerance: A crosscheck hypothesis

Meng-Kun Tsai, Hong-Nerng Ho, Hsiung-Fei Chien, Pu Ou-Yang, Chun-Jean Lee, Po-Huang Lee

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background. The regulatory mechanism by which the B7 ligands (CD80 and CD86) direct the CD28/CD152 costimulatory pathways is unclear. This study investigated the role of CD80 and CD86 in a CD152-mediated allograft tolerance model. Methods. A low-responding cardiac transplant model (BALB/c→B10.A) with possible long-term acceptance was used. Immunocytochemical and flow cytometric analyses of the graft-infiltrating cells were conducted to characterize this transplant model. The influence of anti-CD80 and anti-CD86 treatments on the proliferation and interleukin (IL)-2 productions of the tolerated splenocytes (SC) was analyzed. The role of CD80 and CD86 in the induction and maintenance of the graft acceptance in this transplant model were also tested. Results. B10.A mice could accept the BALA/c cardiac allografts (11/22), and an anti-CD152 antibody blocked the graft acceptance (10/10). Immunocytochemical and flow cytometric analyses showed that CD152+ cells were predominant among the CD4+ cells infiltrating the 100-day grafts of the B10.A recipients (B10.A-100). Either anti-CD80 or anti-CD86 treatment significantly enhanced polyclonal proliferation and IL-2 production of the B10.A-100 SC. Blockade of either CD80 or CD86 prohibited the tolerance transmitted by adoptive transfer, and anti-CD80 or anti-CD86 plus skin grafting undermined the established allograft tolerance. Conclusions. Both CD80 and CD86 were essential for the induction and maintenance of the CD152-mediated allograft tolerance.
Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalTransplantation
Volume77
Issue number1
DOIs
Publication statusPublished - 2004
Externally publishedYes

Fingerprint

Transplantation Tolerance
Ligands
Transplants
Interleukin-2
Maintenance
Skin Transplantation
Adoptive Transfer
Allografts
Anti-Idiotypic Antibodies
Therapeutics

Keywords

  • antigen
  • B7 antigen
  • CD86 antigen
  • cytotoxic T lymphocyte antigen 4
  • interleukin 2
  • unclassified drug
  • allotransplantation
  • animal cell
  • animal experiment
  • animal model
  • antigen function
  • article
  • cell infiltration
  • cell proliferation
  • clinical pathway
  • controlled study
  • cytokine production
  • female
  • flow cytometry
  • heart transplantation
  • immunocytochemistry
  • immunological tolerance
  • long term care
  • mouse
  • nonhuman
  • priority journal
  • regulatory mechanism
  • signal transduction
  • spleen cell
  • Adoptive Transfer
  • Animals
  • Antigens, CD
  • Antigens, CD4
  • Antigens, CD80
  • Antigens, CD86
  • Antigens, Differentiation
  • Cell Division
  • Concanavalin A
  • Female
  • Graft Survival
  • Heart Transplantation
  • Interleukin-2
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred Strains
  • Models, Immunological
  • Monocytes
  • Myocardium
  • Receptors, Interleukin-2
  • Spleen
  • Time Factors
  • Transplantation Tolerance
  • Transplantation, Homologous

Cite this

The role of B7 ligands (CD80 and CD86) in CD152-mediated allograft tolerance: A crosscheck hypothesis. / Tsai, Meng-Kun; Ho, Hong-Nerng; Chien, Hsiung-Fei; Ou-Yang, Pu; Lee, Chun-Jean; Lee, Po-Huang.

In: Transplantation, Vol. 77, No. 1, 2004, p. 48-54.

Research output: Contribution to journalArticle

Tsai, Meng-Kun ; Ho, Hong-Nerng ; Chien, Hsiung-Fei ; Ou-Yang, Pu ; Lee, Chun-Jean ; Lee, Po-Huang. / The role of B7 ligands (CD80 and CD86) in CD152-mediated allograft tolerance: A crosscheck hypothesis. In: Transplantation. 2004 ; Vol. 77, No. 1. pp. 48-54.
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title = "The role of B7 ligands (CD80 and CD86) in CD152-mediated allograft tolerance: A crosscheck hypothesis",
abstract = "Background. The regulatory mechanism by which the B7 ligands (CD80 and CD86) direct the CD28/CD152 costimulatory pathways is unclear. This study investigated the role of CD80 and CD86 in a CD152-mediated allograft tolerance model. Methods. A low-responding cardiac transplant model (BALB/c→B10.A) with possible long-term acceptance was used. Immunocytochemical and flow cytometric analyses of the graft-infiltrating cells were conducted to characterize this transplant model. The influence of anti-CD80 and anti-CD86 treatments on the proliferation and interleukin (IL)-2 productions of the tolerated splenocytes (SC) was analyzed. The role of CD80 and CD86 in the induction and maintenance of the graft acceptance in this transplant model were also tested. Results. B10.A mice could accept the BALA/c cardiac allografts (11/22), and an anti-CD152 antibody blocked the graft acceptance (10/10). Immunocytochemical and flow cytometric analyses showed that CD152+ cells were predominant among the CD4+ cells infiltrating the 100-day grafts of the B10.A recipients (B10.A-100). Either anti-CD80 or anti-CD86 treatment significantly enhanced polyclonal proliferation and IL-2 production of the B10.A-100 SC. Blockade of either CD80 or CD86 prohibited the tolerance transmitted by adoptive transfer, and anti-CD80 or anti-CD86 plus skin grafting undermined the established allograft tolerance. Conclusions. Both CD80 and CD86 were essential for the induction and maintenance of the CD152-mediated allograft tolerance.",
keywords = "antigen, B7 antigen, CD86 antigen, cytotoxic T lymphocyte antigen 4, interleukin 2, unclassified drug, allotransplantation, animal cell, animal experiment, animal model, antigen function, article, cell infiltration, cell proliferation, clinical pathway, controlled study, cytokine production, female, flow cytometry, heart transplantation, immunocytochemistry, immunological tolerance, long term care, mouse, nonhuman, priority journal, regulatory mechanism, signal transduction, spleen cell, Adoptive Transfer, Animals, Antigens, CD, Antigens, CD4, Antigens, CD80, Antigens, CD86, Antigens, Differentiation, Cell Division, Concanavalin A, Female, Graft Survival, Heart Transplantation, Interleukin-2, Membrane Glycoproteins, Mice, Mice, Inbred Strains, Models, Immunological, Monocytes, Myocardium, Receptors, Interleukin-2, Spleen, Time Factors, Transplantation Tolerance, Transplantation, Homologous",
author = "Meng-Kun Tsai and Hong-Nerng Ho and Hsiung-Fei Chien and Pu Ou-Yang and Chun-Jean Lee and Po-Huang Lee",
note = "被引用次數:16 Export Date: 16 March 2016 CODEN: TRPLA 通訊地址: Lee, P.-H.; Department of Surgery, National Taiwan University Hospital, Chung-Shan South Road, Taipei, 100, Taiwan; 電子郵件: pohuang@ha.mc.ntu.edu.tw 化學物質/CAS: interleukin 2, 85898-30-2; Antigens, CD; Antigens, CD4; Antigens, CD80; Antigens, CD86; Antigens, Differentiation; Cd86 protein, mouse; Concanavalin A, 11028-71-0; cytotoxic T-lymphocyte antigen 4; Interleukin-2; Membrane Glycoproteins; Receptors, Interleukin-2 參考文獻: Lenschow, D.J., Walunas, T.L., Bluestone, J.A., CD28/B7 system of T cell costimulation (1996) Annu Rev Immunol, 14, p. 233; Salomon, B., Bluestone, J.A., Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation (2001) Annu Rev Immunol, 19, p. 225; 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, p. 1352; 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, p. 541; Waterhouse, P., Penninger, J., Timms, E., Lymproliferative disorders with early lethality in mice deficient in CTLA-4 (1995) Science, 270, p. 985; Perez, V.L., Van Parijis, L., Biuckians, A., Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement (1997) Immunity, 6, p. 411; Walunas, T.L., Bluestone, J.A., CTLA-4 regulates tolerance induction and T cell differentiation in vivo (1998) J Immunol, 160, p. 3855; Fecteau, S., Basadonna, G.P., Freitas, A., CTLA-4 up-regulation plays a role in tolerance mediated by CD45 (2001) Nat Immunol, 2, p. 58; Read, S., Malmstrom, V., Powrie, F., Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation (2000) J Exp Med, 192, p. 295; Takahashi, T., Tagami, T., Yamazaki, S., Immunological self-tolerance maintained by CD25+CD4 + regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4 (2000) J Exp Med, 192, p. 303; Bour-Jordan, H., Bluestone, J.A., CD28 function: A balance of costimulatory and regulatory signals (2002) J Clin Immunol, 22, p. 1; Collins, A.V., Brodie, D.W., Gilbert, R.J., The interaction properties of costimulatory molecules revisited (2002) Immunity, 17, p. 201; Egen, J.G., Kuhns, M.S., Allison, J.P., CTLA-4: New insights into its biological function and use in tumor immunotherapy (2002) Nat Immunol, 3, p. 611; 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, p. 1947; 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, p. 3037; Chen, Z., A technique of cervical heterotopic heart transplantation in mice (1991) Transplantation, 52, p. 1099; Ho, H.N., Chao, K.H., Chen, C.K., The activation status of T and NK cells in the endometrium throughout menstrual cycle and normal and abnormal early pregnancy (1996) Hum Immunol, 49, p. 130; 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, p. 39; 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; Qin, S., Cobbold, S.P., Pope, H., {"}Infectious{"} transplantation tolerance (1993) Science, 259, p. 974; Cobbold, S., Waldmann, H., Infectious tolerance (1998) Curr Opin Immunol, 10, p. 518; Li, X.C., Strom, T.B., Turka, L.A., T cell death and transplantation tolerance (2001) Immunity, 14, p. 407; 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, p. 4762; 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, p. 2444; Greenwald, R.J., Oosterwegel, M.A., Van Der Woude, D., CTLA-4 regulates cell cycle progression during a primary immune response (2002) Eur J Immunol, 32, p. 366; Bachmann, M.F., Kohler, G., Ecabert, B., Cutting edge: Lymphoproliferative disease in the absence of CTLA-4 in not T cell autonomous (1999) J Immunol, 163, p. 1128; Chambers, C.A., Kuhns, M.S., Egen, J.G., CTLA-4-mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy (2001) Annu Rev Immunol, 19, p. 565; Eagar, T.N., Karandikar, N.J., Bluestone, J.A., The role of CTLA-4 in induction and maintenance of peripheral T cell tolerance (2002) Eur J Immunol, 32, p. 972",
year = "2004",
doi = "10.1097/01.TP.0000107286.21985.EF",
language = "English",
volume = "77",
pages = "48--54",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - The role of B7 ligands (CD80 and CD86) in CD152-mediated allograft tolerance: A crosscheck hypothesis

AU - Tsai, Meng-Kun

AU - Ho, Hong-Nerng

AU - Chien, Hsiung-Fei

AU - Ou-Yang, Pu

AU - Lee, Chun-Jean

AU - Lee, Po-Huang

N1 - 被引用次數:16 Export Date: 16 March 2016 CODEN: TRPLA 通訊地址: Lee, P.-H.; Department of Surgery, National Taiwan University Hospital, Chung-Shan South Road, Taipei, 100, Taiwan; 電子郵件: pohuang@ha.mc.ntu.edu.tw 化學物質/CAS: interleukin 2, 85898-30-2; Antigens, CD; Antigens, CD4; Antigens, CD80; Antigens, CD86; Antigens, Differentiation; Cd86 protein, mouse; Concanavalin A, 11028-71-0; cytotoxic T-lymphocyte antigen 4; Interleukin-2; Membrane Glycoproteins; Receptors, Interleukin-2 參考文獻: Lenschow, D.J., Walunas, T.L., Bluestone, J.A., CD28/B7 system of T cell costimulation (1996) Annu Rev Immunol, 14, p. 233; Salomon, B., Bluestone, J.A., Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation (2001) Annu Rev Immunol, 19, p. 225; 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, p. 1352; 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, p. 541; Waterhouse, P., Penninger, J., Timms, E., Lymproliferative disorders with early lethality in mice deficient in CTLA-4 (1995) Science, 270, p. 985; Perez, V.L., Van Parijis, L., Biuckians, A., Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement (1997) Immunity, 6, p. 411; Walunas, T.L., Bluestone, J.A., CTLA-4 regulates tolerance induction and T cell differentiation in vivo (1998) J Immunol, 160, p. 3855; Fecteau, S., Basadonna, G.P., Freitas, A., CTLA-4 up-regulation plays a role in tolerance mediated by CD45 (2001) Nat Immunol, 2, p. 58; Read, S., Malmstrom, V., Powrie, F., Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation (2000) J Exp Med, 192, p. 295; Takahashi, T., Tagami, T., Yamazaki, S., Immunological self-tolerance maintained by CD25+CD4 + regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4 (2000) J Exp Med, 192, p. 303; Bour-Jordan, H., Bluestone, J.A., CD28 function: A balance of costimulatory and regulatory signals (2002) J Clin Immunol, 22, p. 1; Collins, A.V., Brodie, D.W., Gilbert, R.J., The interaction properties of costimulatory molecules revisited (2002) Immunity, 17, p. 201; Egen, J.G., Kuhns, M.S., Allison, J.P., CTLA-4: New insights into its biological function and use in tumor immunotherapy (2002) Nat Immunol, 3, p. 611; 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, p. 1947; 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, p. 3037; Chen, Z., A technique of cervical heterotopic heart transplantation in mice (1991) Transplantation, 52, p. 1099; Ho, H.N., Chao, K.H., Chen, C.K., The activation status of T and NK cells in the endometrium throughout menstrual cycle and normal and abnormal early pregnancy (1996) Hum Immunol, 49, p. 130; 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, p. 39; 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; Qin, S., Cobbold, S.P., Pope, H., "Infectious" transplantation tolerance (1993) Science, 259, p. 974; Cobbold, S., Waldmann, H., Infectious tolerance (1998) Curr Opin Immunol, 10, p. 518; Li, X.C., Strom, T.B., Turka, L.A., T cell death and transplantation tolerance (2001) Immunity, 14, p. 407; 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, p. 4762; 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, p. 2444; Greenwald, R.J., Oosterwegel, M.A., Van Der Woude, D., CTLA-4 regulates cell cycle progression during a primary immune response (2002) Eur J Immunol, 32, p. 366; Bachmann, M.F., Kohler, G., Ecabert, B., Cutting edge: Lymphoproliferative disease in the absence of CTLA-4 in not T cell autonomous (1999) J Immunol, 163, p. 1128; Chambers, C.A., Kuhns, M.S., Egen, J.G., CTLA-4-mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy (2001) Annu Rev Immunol, 19, p. 565; Eagar, T.N., Karandikar, N.J., Bluestone, J.A., The role of CTLA-4 in induction and maintenance of peripheral T cell tolerance (2002) Eur J Immunol, 32, p. 972

PY - 2004

Y1 - 2004

N2 - Background. The regulatory mechanism by which the B7 ligands (CD80 and CD86) direct the CD28/CD152 costimulatory pathways is unclear. This study investigated the role of CD80 and CD86 in a CD152-mediated allograft tolerance model. Methods. A low-responding cardiac transplant model (BALB/c→B10.A) with possible long-term acceptance was used. Immunocytochemical and flow cytometric analyses of the graft-infiltrating cells were conducted to characterize this transplant model. The influence of anti-CD80 and anti-CD86 treatments on the proliferation and interleukin (IL)-2 productions of the tolerated splenocytes (SC) was analyzed. The role of CD80 and CD86 in the induction and maintenance of the graft acceptance in this transplant model were also tested. Results. B10.A mice could accept the BALA/c cardiac allografts (11/22), and an anti-CD152 antibody blocked the graft acceptance (10/10). Immunocytochemical and flow cytometric analyses showed that CD152+ cells were predominant among the CD4+ cells infiltrating the 100-day grafts of the B10.A recipients (B10.A-100). Either anti-CD80 or anti-CD86 treatment significantly enhanced polyclonal proliferation and IL-2 production of the B10.A-100 SC. Blockade of either CD80 or CD86 prohibited the tolerance transmitted by adoptive transfer, and anti-CD80 or anti-CD86 plus skin grafting undermined the established allograft tolerance. Conclusions. Both CD80 and CD86 were essential for the induction and maintenance of the CD152-mediated allograft tolerance.

AB - Background. The regulatory mechanism by which the B7 ligands (CD80 and CD86) direct the CD28/CD152 costimulatory pathways is unclear. This study investigated the role of CD80 and CD86 in a CD152-mediated allograft tolerance model. Methods. A low-responding cardiac transplant model (BALB/c→B10.A) with possible long-term acceptance was used. Immunocytochemical and flow cytometric analyses of the graft-infiltrating cells were conducted to characterize this transplant model. The influence of anti-CD80 and anti-CD86 treatments on the proliferation and interleukin (IL)-2 productions of the tolerated splenocytes (SC) was analyzed. The role of CD80 and CD86 in the induction and maintenance of the graft acceptance in this transplant model were also tested. Results. B10.A mice could accept the BALA/c cardiac allografts (11/22), and an anti-CD152 antibody blocked the graft acceptance (10/10). Immunocytochemical and flow cytometric analyses showed that CD152+ cells were predominant among the CD4+ cells infiltrating the 100-day grafts of the B10.A recipients (B10.A-100). Either anti-CD80 or anti-CD86 treatment significantly enhanced polyclonal proliferation and IL-2 production of the B10.A-100 SC. Blockade of either CD80 or CD86 prohibited the tolerance transmitted by adoptive transfer, and anti-CD80 or anti-CD86 plus skin grafting undermined the established allograft tolerance. Conclusions. Both CD80 and CD86 were essential for the induction and maintenance of the CD152-mediated allograft tolerance.

KW - antigen

KW - B7 antigen

KW - CD86 antigen

KW - cytotoxic T lymphocyte antigen 4

KW - interleukin 2

KW - unclassified drug

KW - allotransplantation

KW - animal cell

KW - animal experiment

KW - animal model

KW - antigen function

KW - article

KW - cell infiltration

KW - cell proliferation

KW - clinical pathway

KW - controlled study

KW - cytokine production

KW - female

KW - flow cytometry

KW - heart transplantation

KW - immunocytochemistry

KW - immunological tolerance

KW - long term care

KW - mouse

KW - nonhuman

KW - priority journal

KW - regulatory mechanism

KW - signal transduction

KW - spleen cell

KW - Adoptive Transfer

KW - Animals

KW - Antigens, CD

KW - Antigens, CD4

KW - Antigens, CD80

KW - Antigens, CD86

KW - Antigens, Differentiation

KW - Cell Division

KW - Concanavalin A

KW - Female

KW - Graft Survival

KW - Heart Transplantation

KW - Interleukin-2

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, Inbred Strains

KW - Models, Immunological

KW - Monocytes

KW - Myocardium

KW - Receptors, Interleukin-2

KW - Spleen

KW - Time Factors

KW - Transplantation Tolerance

KW - Transplantation, Homologous

U2 - 10.1097/01.TP.0000107286.21985.EF

DO - 10.1097/01.TP.0000107286.21985.EF

M3 - Article

VL - 77

SP - 48

EP - 54

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 1

ER -