Skip to main content
Top
Published in: Immunologic Research 3/2012

01-06-2012

A role for anti-CD45RB monoclonal antibody treatment upon dendritic cells

Authors: Hui Qi, Jin-Peng Liu, Chun-Yan Deng, Han-Xin Zhou, Shao-Ping Deng, Fu-Rong Li

Published in: Immunologic Research | Issue 3/2012

Login to get access

Abstract

Selective interference with CD45RB isoform by monoclonal antibody (anti-CD45RBmAb) reliably induces donor-specific tolerance. Dendritic cells (DCs) are the most potent antigen-presenting cells that are capable of activating naïve T cells. The purposes of the present study were to investigate the roles of anti-CD45RBmAb on the phenotypes and functioning of DCs and to further illustrate the mechanism of anti-CD45RBmAb-inducing immunologic tolerance. DCs from C57BL/6 mice were cultured and treated with various doses of anti-CD45RB monoclonal antibody. Cell phenotype, cycle and phagocytic ability were detected by flow cytometry. The production of IL-10 and IL-12 in the supernatants of mature DCs was measured with ELISA. Exosomes (Dex) were recovered from the supernatant of DCs cultured for 6 days in depleted medium, and effects of DCs and Dex on the ability of T-cell proliferation were detected by mixed lymphocyte culture. Anti-CD45RBmAb could inhibit DCs maturation in a dose-dependent manner, and the effects of exosomes (Dex) on DCs enhance or inhibition proliferation of T cells were also in a dose-dependent manner. Anti-CD45RBmAb could profoundly inhibit the maturation and functioning of DCs and generate tolerogenic dendritic cells (tDCs) as well as Dex, suggesting mechanistic contributions to tolerance development from the DCs through interactions with T cells.
Literature
1.
go back to reference Koretzky GA, Picus J, Schultz T, Weiss A. Tyrosine phosphatase CD45 is required for T-cell antigen receptor and CD2-mediated activation of a protein tyrosine kinase and interleukin 2 production. PNAS. 1991;88:2037.PubMedCrossRef Koretzky GA, Picus J, Schultz T, Weiss A. Tyrosine phosphatase CD45 is required for T-cell antigen receptor and CD2-mediated activation of a protein tyrosine kinase and interleukin 2 production. PNAS. 1991;88:2037.PubMedCrossRef
2.
go back to reference Irie-Sasaki J, Sasaki T, Matsumoto W, et al. CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling. Nature. 2001;409:349.PubMedCrossRef Irie-Sasaki J, Sasaki T, Matsumoto W, et al. CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling. Nature. 2001;409:349.PubMedCrossRef
3.
go back to reference Justement LB. The role of the protein tyrosine phosphatase CD45 in regulation of B lymphocyte activation. Int Rev Immunol. 2001;20:713.PubMedCrossRef Justement LB. The role of the protein tyrosine phosphatase CD45 in regulation of B lymphocyte activation. Int Rev Immunol. 2001;20:713.PubMedCrossRef
4.
go back to reference Zhang Z, Lazarovits A, Grant D, Garcia B, Stiller C. Zhong R.CD45RB monoclonal antibody induces tolerance in the mouse kidney graft, but fails to prevent small bowel graft rejection. Transplant Proc. 1996;28:2514.PubMed Zhang Z, Lazarovits A, Grant D, Garcia B, Stiller C. Zhong R.CD45RB monoclonal antibody induces tolerance in the mouse kidney graft, but fails to prevent small bowel graft rejection. Transplant Proc. 1996;28:2514.PubMed
5.
go back to reference Auersvald LA, Rothstein DM, Oliveira SC, et al. Indefinite islet allograft survival in mice after a short course of treatment with anti-CD45 monoclonal antibodies. Transplantation. 1997;63:1355.PubMedCrossRef Auersvald LA, Rothstein DM, Oliveira SC, et al. Indefinite islet allograft survival in mice after a short course of treatment with anti-CD45 monoclonal antibodies. Transplantation. 1997;63:1355.PubMedCrossRef
6.
go back to reference Auersvald LA, Rothstein DM, Oliveira SC, Khuong CQ, Basadonna GP. Anti-CD45RB treatment prolongs islet allograft survival in mice. Transplant Proc. 1997;29:771.PubMedCrossRef Auersvald LA, Rothstein DM, Oliveira SC, Khuong CQ, Basadonna GP. Anti-CD45RB treatment prolongs islet allograft survival in mice. Transplant Proc. 1997;29:771.PubMedCrossRef
7.
go back to reference Basadonna GP, Auersvald L, Khuong CQ, et al. Antibody-mediated targeting of CD45 isoforms: a novel immunotherapeutic strategy. PNAS. 1998;95:3821.PubMedCrossRef Basadonna GP, Auersvald L, Khuong CQ, et al. Antibody-mediated targeting of CD45 isoforms: a novel immunotherapeutic strategy. PNAS. 1998;95:3821.PubMedCrossRef
8.
go back to reference Deng S, Moore DJ, Huang X, et al. Antibody-induced transplantation tolerance that is dependent on thymus-derived regulatory T cells. J Immunol. 2006;176:2799.PubMed Deng S, Moore DJ, Huang X, et al. Antibody-induced transplantation tolerance that is dependent on thymus-derived regulatory T cells. J Immunol. 2006;176:2799.PubMed
9.
go back to reference Deng S, Moore DJ, Huang X, et al. Cutting edge: transplant tolerance induced by anti-CD45RB requires B lymphocytes. J Immunol. 2007;178:6028.PubMed Deng S, Moore DJ, Huang X, et al. Cutting edge: transplant tolerance induced by anti-CD45RB requires B lymphocytes. J Immunol. 2007;178:6028.PubMed
10.
go back to reference Walunas TL, Lenschow DJ, Bakker CY, et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994;1:405.PubMedCrossRef Walunas TL, Lenschow DJ, Bakker CY, et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994;1:405.PubMedCrossRef
11.
go back to reference Tisch R. Immunogenic versus tolerogenic dendritic cells: a matter of maturation. Int Rev Immunol. 2010;29:111.PubMedCrossRef Tisch R. Immunogenic versus tolerogenic dendritic cells: a matter of maturation. Int Rev Immunol. 2010;29:111.PubMedCrossRef
12.
go back to reference Min WP, Zhou D, Ichim TE, et al. Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance. Immunology. 2003;170:1304. Min WP, Zhou D, Ichim TE, et al. Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance. Immunology. 2003;170:1304.
13.
go back to reference Smith M, Bittner JG 4th, White S, et al. HLA-G-treated tolerogenic dendritic cells induce tolerogenic potential by increasing expression of B7–1 (CD80) molecules. Transplant Proc. 2008;40:1598.PubMedCrossRef Smith M, Bittner JG 4th, White S, et al. HLA-G-treated tolerogenic dendritic cells induce tolerogenic potential by increasing expression of B7–1 (CD80) molecules. Transplant Proc. 2008;40:1598.PubMedCrossRef
14.
go back to reference Li M, Zhang X, Zheng X, et al. Tolerogenic dendritic cells transferring hyporesponsiveness and synergizing T regulatory cells in transplant tolerance. Int Immunol. 2008;20:285.PubMedCrossRef Li M, Zhang X, Zheng X, et al. Tolerogenic dendritic cells transferring hyporesponsiveness and synergizing T regulatory cells in transplant tolerance. Int Immunol. 2008;20:285.PubMedCrossRef
15.
go back to reference Segura E, Nicco C, Lombard B, et al. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood. 2005;106:216.PubMedCrossRef Segura E, Nicco C, Lombard B, et al. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood. 2005;106:216.PubMedCrossRef
16.
go back to reference Viaud S, Terme M, Flament C, et al. Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: a role for NKG2D ligands and IL-15Ralpha. PLoS ONE. 2009;4:e4942.PubMedCrossRef Viaud S, Terme M, Flament C, et al. Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: a role for NKG2D ligands and IL-15Ralpha. PLoS ONE. 2009;4:e4942.PubMedCrossRef
17.
go back to reference Dai S, Wei D, Wu Z, et al. Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Mol Ther. 2008;16:782.PubMedCrossRef Dai S, Wei D, Wu Z, et al. Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Mol Ther. 2008;16:782.PubMedCrossRef
18.
go back to reference Pêche H, Renaudin K, Beriou G, et al. Induction of tolerance by exosomes and short-term immunosuppression in a fully MHC-mismatched rat cardiac allograft model. Am J Transplant. 2006;6:1541.PubMedCrossRef Pêche H, Renaudin K, Beriou G, et al. Induction of tolerance by exosomes and short-term immunosuppression in a fully MHC-mismatched rat cardiac allograft model. Am J Transplant. 2006;6:1541.PubMedCrossRef
19.
go back to reference Sallusto F, Cella M, Danieli C, Lanzavecchia A. Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995;182:389.PubMedCrossRef Sallusto F, Cella M, Danieli C, Lanzavecchia A. Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995;182:389.PubMedCrossRef
20.
go back to reference Lamparski HG, Metha-Damani A, Yao JY, et al. Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods. 2002;270:211.PubMedCrossRef Lamparski HG, Metha-Damani A, Yao JY, et al. Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods. 2002;270:211.PubMedCrossRef
21.
go back to reference Banchereau J, Steinman RM, Banchereall J. et al.Dendritic cells and the control of immunity. Nature. 1998;392:245.PubMedCrossRef Banchereau J, Steinman RM, Banchereall J. et al.Dendritic cells and the control of immunity. Nature. 1998;392:245.PubMedCrossRef
22.
go back to reference Aerts-Toegaert C, Heirman C, Tuyaerts S, et al. CD83 expression on dendritic cells and T cells: correlation with effective immune responses. Eur J Immunol. 2007;37:686.PubMedCrossRef Aerts-Toegaert C, Heirman C, Tuyaerts S, et al. CD83 expression on dendritic cells and T cells: correlation with effective immune responses. Eur J Immunol. 2007;37:686.PubMedCrossRef
23.
go back to reference Chang HW, Chow YH, Chong P, et al. The cross-regulatory relationship between human dendritic and regulatory T cells and its role in type 1 diabetes mellitus. Rev Diabet Stud. 2007;4:68.PubMedCrossRef Chang HW, Chow YH, Chong P, et al. The cross-regulatory relationship between human dendritic and regulatory T cells and its role in type 1 diabetes mellitus. Rev Diabet Stud. 2007;4:68.PubMedCrossRef
24.
go back to reference Billiard F, Litvinova E, Saadoun D, et al. Regulatory and effector T cell activation levels are prime determinants of in vivo immune regulation. J Immunol. 2006;177:2167.PubMed Billiard F, Litvinova E, Saadoun D, et al. Regulatory and effector T cell activation levels are prime determinants of in vivo immune regulation. J Immunol. 2006;177:2167.PubMed
25.
go back to reference Commeren DL, Van Soest PL, Karimi K, et al. Paradoxical effects of interleukin-10 on the maturation of murine myeloid dendritic cells. Immunology. 2003;110:188. [PubMed: 14511232].PubMedCrossRef Commeren DL, Van Soest PL, Karimi K, et al. Paradoxical effects of interleukin-10 on the maturation of murine myeloid dendritic cells. Immunology. 2003;110:188. [PubMed: 14511232].PubMedCrossRef
26.
go back to reference Geissmann F, Manz MG, Jung S, et al. Development of monocytes, macrophages, and dendritic cells. Science. 2010;327:656.PubMedCrossRef Geissmann F, Manz MG, Jung S, et al. Development of monocytes, macrophages, and dendritic cells. Science. 2010;327:656.PubMedCrossRef
27.
go back to reference Winzler C, Rovere P, Rescigno M, et al. Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J Exp Med. 1997;185:317.PubMedCrossRef Winzler C, Rovere P, Rescigno M, et al. Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J Exp Med. 1997;185:317.PubMedCrossRef
28.
go back to reference Cools N, Van Tendeloo VF, Smits EL, Lenjou M, Nijs G, Van Bockstaele DR, Berneman ZN, Ponsaerts P. Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4 + regulatory T cells. J Cell Mol Med. 2008;12:690–700.PubMedCrossRef Cools N, Van Tendeloo VF, Smits EL, Lenjou M, Nijs G, Van Bockstaele DR, Berneman ZN, Ponsaerts P. Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4 + regulatory T cells. J Cell Mol Med. 2008;12:690–700.PubMedCrossRef
29.
go back to reference Messmer D, Hatsukari I, Hitosugi N, Schmidt-Wolf IG, Singhal PC. Morphine reciprocally regulates IL-10 and IL-12 production by monocyte-derived human dendritic cells and enhances T cell activation. Mol Med. 2006;12(11–12):284–90.PubMed Messmer D, Hatsukari I, Hitosugi N, Schmidt-Wolf IG, Singhal PC. Morphine reciprocally regulates IL-10 and IL-12 production by monocyte-derived human dendritic cells and enhances T cell activation. Mol Med. 2006;12(11–12):284–90.PubMed
30.
go back to reference Kim SH, Bianco N, Menon R, et al. Exosomes derived from genetically modified DC expressing FasL are anti-inflammatory and immunosuppressive. Mol Ther. 2006;13:289. [PubMed: 16275099].PubMedCrossRef Kim SH, Bianco N, Menon R, et al. Exosomes derived from genetically modified DC expressing FasL are anti-inflammatory and immunosuppressive. Mol Ther. 2006;13:289. [PubMed: 16275099].PubMedCrossRef
31.
go back to reference Kim SH, Kim S, Evans CH, Ghivizzani SC, Oligino T, Robbins PD. Effective treatment of established murine collagen-induced arthritis by systemic administration of dendritic cells genetically modified to express IL-4. J Immuno. 2001;166:3499. Kim SH, Kim S, Evans CH, Ghivizzani SC, Oligino T, Robbins PD. Effective treatment of established murine collagen-induced arthritis by systemic administration of dendritic cells genetically modified to express IL-4. J Immuno. 2001;166:3499.
Metadata
Title
A role for anti-CD45RB monoclonal antibody treatment upon dendritic cells
Authors
Hui Qi
Jin-Peng Liu
Chun-Yan Deng
Han-Xin Zhou
Shao-Ping Deng
Fu-Rong Li
Publication date
01-06-2012
Publisher
Springer-Verlag
Published in
Immunologic Research / Issue 3/2012
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-012-8336-0

Other articles of this Issue 3/2012

Immunologic Research 3/2012 Go to the issue