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Endothelial cells present antigens in vivo

BACKGROUND: Immune recognition of vascular endothelial cells (EC) has been implicated in allograft rejection, protection against pathogens, and lymphocyte recruitment. However, EC pervade nearly all tissues and predominate in none, complicating any direct test of immune recognition. Here, we examine...

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Autores principales: Rothermel, Annette L, Wang, Yinong, Schechner, Jeffrey, Mook-Kanamori, Barry, Aird, William C, Pober, Jordan S, Tellides, George, Johnson, David R
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC394319/
https://www.ncbi.nlm.nih.gov/pubmed/15113397
http://dx.doi.org/10.1186/1471-2172-5-5
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author Rothermel, Annette L
Wang, Yinong
Schechner, Jeffrey
Mook-Kanamori, Barry
Aird, William C
Pober, Jordan S
Tellides, George
Johnson, David R
author_facet Rothermel, Annette L
Wang, Yinong
Schechner, Jeffrey
Mook-Kanamori, Barry
Aird, William C
Pober, Jordan S
Tellides, George
Johnson, David R
author_sort Rothermel, Annette L
collection PubMed
description BACKGROUND: Immune recognition of vascular endothelial cells (EC) has been implicated in allograft rejection, protection against pathogens, and lymphocyte recruitment. However, EC pervade nearly all tissues and predominate in none, complicating any direct test of immune recognition. Here, we examined antigen presentation by EC in vivo by testing immune responses against E. coli β-galactosidase (β-gal) in two lines of transgenic mice that express β-gal exclusively in their EC. TIE2-lacZ mice express β-gal in all EC and VWF-lacZ mice express β-gal in heart and brain microvascular EC. RESULTS: Transgenic and congenic wild type FVB mice immunized with β-gal expression vector DNA or β-gal protein generated high titer, high affinity antisera containing comparable levels of antigen-specific IgG1 and IgG2a isotypes, suggesting equivalent activation of T helper cell subsets. The immunized transgenic mice remained healthy, their EC continued to express β-gal, and their blood vessels showed no histological abnormalities. In response to β-gal in vitro, CD4(+ )and CD8(+ )T cells from immunized transgenic and FVB mice proliferated, expressed CD25, and secreted IFN-γ. Infection with recombinant vaccinia virus encoding β-gal raised equivalent responses in transgenic and FVB mice. Hearts transplanted from transgenic mice into FVB mice continued to beat and the graft EC continued to express β-gal. These results suggested immunological ignorance of the transgene encoded EC protein. However, skin transplanted from TIE2-lacZ onto FVB mice lost β-gal(+ )EC and the hosts developed β-gal-specific antisera, demonstrating activation of host immune effector mechanisms. In contrast, skin grafted from TIE2-lacZ onto VWF-lacZ mice retained β-gal(+ )EC and no antisera developed, suggesting a tolerant host immune system. CONCLUSION: Resting, β-gal(+ )EC in transgenic mice tolerize specific lymphocytes that would otherwise respond against β-gal expressed by EC within transplanted skin. We conclude that EC effectively present intracellular "self" proteins to the immune system. However, antigen presentation by EC does not delete or anergize a large population of specific lymphocytes that respond to the same protein following conventional immunization with protein or expression vector DNA. These results clearly demonstrate striking context sensitivity in the immune recognition of EC, a subtlety that must be better understood in order to treat immune diseases and complications involving the vasculature.
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spelling pubmed-3943192004-04-22 Endothelial cells present antigens in vivo Rothermel, Annette L Wang, Yinong Schechner, Jeffrey Mook-Kanamori, Barry Aird, William C Pober, Jordan S Tellides, George Johnson, David R BMC Immunol Research Article BACKGROUND: Immune recognition of vascular endothelial cells (EC) has been implicated in allograft rejection, protection against pathogens, and lymphocyte recruitment. However, EC pervade nearly all tissues and predominate in none, complicating any direct test of immune recognition. Here, we examined antigen presentation by EC in vivo by testing immune responses against E. coli β-galactosidase (β-gal) in two lines of transgenic mice that express β-gal exclusively in their EC. TIE2-lacZ mice express β-gal in all EC and VWF-lacZ mice express β-gal in heart and brain microvascular EC. RESULTS: Transgenic and congenic wild type FVB mice immunized with β-gal expression vector DNA or β-gal protein generated high titer, high affinity antisera containing comparable levels of antigen-specific IgG1 and IgG2a isotypes, suggesting equivalent activation of T helper cell subsets. The immunized transgenic mice remained healthy, their EC continued to express β-gal, and their blood vessels showed no histological abnormalities. In response to β-gal in vitro, CD4(+ )and CD8(+ )T cells from immunized transgenic and FVB mice proliferated, expressed CD25, and secreted IFN-γ. Infection with recombinant vaccinia virus encoding β-gal raised equivalent responses in transgenic and FVB mice. Hearts transplanted from transgenic mice into FVB mice continued to beat and the graft EC continued to express β-gal. These results suggested immunological ignorance of the transgene encoded EC protein. However, skin transplanted from TIE2-lacZ onto FVB mice lost β-gal(+ )EC and the hosts developed β-gal-specific antisera, demonstrating activation of host immune effector mechanisms. In contrast, skin grafted from TIE2-lacZ onto VWF-lacZ mice retained β-gal(+ )EC and no antisera developed, suggesting a tolerant host immune system. CONCLUSION: Resting, β-gal(+ )EC in transgenic mice tolerize specific lymphocytes that would otherwise respond against β-gal expressed by EC within transplanted skin. We conclude that EC effectively present intracellular "self" proteins to the immune system. However, antigen presentation by EC does not delete or anergize a large population of specific lymphocytes that respond to the same protein following conventional immunization with protein or expression vector DNA. These results clearly demonstrate striking context sensitivity in the immune recognition of EC, a subtlety that must be better understood in order to treat immune diseases and complications involving the vasculature. BioMed Central 2004-03-16 /pmc/articles/PMC394319/ /pubmed/15113397 http://dx.doi.org/10.1186/1471-2172-5-5 Text en Copyright © 2004 Rothermel et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
spellingShingle Research Article
Rothermel, Annette L
Wang, Yinong
Schechner, Jeffrey
Mook-Kanamori, Barry
Aird, William C
Pober, Jordan S
Tellides, George
Johnson, David R
Endothelial cells present antigens in vivo
title Endothelial cells present antigens in vivo
title_full Endothelial cells present antigens in vivo
title_fullStr Endothelial cells present antigens in vivo
title_full_unstemmed Endothelial cells present antigens in vivo
title_short Endothelial cells present antigens in vivo
title_sort endothelial cells present antigens in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC394319/
https://www.ncbi.nlm.nih.gov/pubmed/15113397
http://dx.doi.org/10.1186/1471-2172-5-5
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