Home LiteratureArticle Details
PMID: 12391021 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The CD8alpha(+) dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens.

The Journal of experimental medicine ·Vol. 196 ·No. 8 ·2002-10-21 ·Pages 1099-104

Belz GT, Behrens GM, Smith CM, Miller JF, Jones C, Lejon K, Fathman CG, Mueller SN, Shortman K, Carbone FR, Heath WR

Abstract

We previously described a mechanism for the maintenance of peripheral self-tolerance. This involves the cross-presentation of tissue-associated antigens by a bone marrow-derived cell type that stimulates the proliferation and ultimate deletion of self-reactive CD8 T cells. This process has been referred to as cross-tolerance. Here, we characterize the elusive cell type responsible for inducing cross-tolerance as a CD8alpha(+) dendritic cell (DC). To achieve this aim, transgenic mice were generated expressing yellow fluorescent protein (YFP) linked to CTL epitopes for ovalbumin and glycoprotein B (gB) of herpes simplex virus under the rat insulin promoter (RIP). Although tracking of YFP was inconclusive, the use of a highly sensitive gB-specific hybridoma that produced beta-galactosidase on encounter with antigen, enabled detection of antigen presentation by cells isolated from the pancreatic lymph node. This showed that a CD11c(+)CD8alpha(+) cell was responsible for cross-tolerance, the same DC subset as previously implicated in cross-priming. These data indicate that CD8alpha(+) DCs play a critical role in both tolerance and immunity to cell-associated antigens, providing a potential mechanism by which cytotoxic T lymphocyte can be immunized to viral antigens while maintaining tolerance to self.

MeSH Terms
Animals Antigens, CD/immunology Bacterial Proteins/genetics Base Sequence CD8-Positive T-Lymphocytes/immunology DNA Primers Immune Tolerance Immunophenotyping Insulin/genetics Luminescent Proteins/genetics Mice Mice, Transgenic Promoter Regions, Genetic Rats
Chemicals
Antigens, CD Bacterial Proteins DNA Primers Insulin Luminescent Proteins yellow fluorescent protein, Bacteria
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Belz Gabrielle T
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia. [email protected]
Behrens Georg M N
Smith Chris M
Miller Jacques F A P
Jones Claerwen
Lejon Kristina
Fathman C Garrison
Mueller Scott N
Shortman Ken
Carbone Francis R
Heath William R
References (29)
29 references, click to expand
  1. CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T cells in vivo.
    J Exp Med. 2000 Dec 18;192(12):1685-96 PMID: 11120766
  2. Selecting and maintaining a diverse T-cell repertoire.
    Nature. 1999 Nov 18;402(6759):255-62 PMID: 10580495
  3. Cross-presentation, dendritic cells, tolerance and immunity.
    Annu Rev Immunol. 2001;19:47-64 PMID: 11244030
  4. Cell-associated ovalbumin is cross-presented much more efficiently than soluble ovalbumin in vivo.
    J Immunol. 2001 May 15;166(10):6099-103 PMID: 11342628
  5. The dendritic cell populations of mouse lymph nodes.
    J Immunol. 2001 Jul 15;167(2):741-8 PMID: 11441078
  6. Class I-restricted cross-presentation of exogenous self-antigens leads to deletion of autoreactive CD8(+) T cells.
    J Exp Med. 1997 Jul 21;186(2):239-45 PMID: 9221753
  7. Help for cytotoxic-T-cell responses is mediated by CD40 signalling.
    Nature. 1998 Jun 4;393(6684):478-80 PMID: 9624004
  8. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions.
    Nature. 1998 Jun 4;393(6684):480-3 PMID: 9624005
  9. Major histocompatibility complex class I-restricted cross-presentation is biased towards high dose antigens and those released during cellular destruction.
    J Exp Med. 1998 Jul 20;188(2):409-14 PMID: 9670054
  10. Induction of peripheral CD8+ T-cell tolerance by cross-presentation of self antigens.
    Immunol Rev. 1998 Oct;165:267-77 PMID: 9850866
  11. Dendritic cells are sufficient to cross-present self-antigens to CD8 T cells in vivo.
    J Immunol. 2001 Feb 1;166(3):1439-42 PMID: 11160180
  12. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo.
    J Exp Med. 2001 Sep 17;194(6):769-79 PMID: 11560993
  13. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance.
    Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):351-8 PMID: 11773639
  14. Tolerance to islet antigens and prevention from diabetes induced by limited apoptosis of pancreatic beta cells.
    Immunity. 2002 Feb;16(2):169-81 PMID: 11869679
  15. Rapid cytotoxic T lymphocyte activation occurs in the draining lymph nodes after cutaneous herpes simplex virus infection as a result of early antigen presentation and not the presence of virus.
    J Exp Med. 2002 Mar 4;195(5):651-6 PMID: 11877488
  16. Cross-presentation in viral immunity and self-tolerance.
    Nat Rev Immunol. 2001 Nov;1(2):126-34 PMID: 11905820
  17. Characterization of two TCR transgenic mouse lines specific for herpes simplex virus.
    Immunol Cell Biol. 2002 Apr;80(2):156-63 PMID: 11940116
  18. CD8alpha- CD11b+ dendritic cells present exogenous virus-like particles to CD8+ T cells and subsequently express CD8alpha and CD205 molecules.
    J Exp Med. 2002 May 20;195(10):1233-45 PMID: 12021304
  19. The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo.
    J Exp Med. 2002 May 20;195(10):1289-302 PMID: 12021309
  20. Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay.
    J Exp Med. 1976 May 1;143(5):1283-8 PMID: 1083422
  21. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo.
    J Exp Med. 1987 Feb 1;165(2):302-19 PMID: 3029267
  22. The immune system evolved to discriminate infectious nonself from noninfectious self.
    Immunol Today. 1992 Jan;13(1):11-6 PMID: 1739426
  23. The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells.
    J Exp Med. 1992 Jul 1;176(1):47-58 PMID: 1613465
  24. Detection of rare antigen-presenting cells by the lacZ T-cell activation assay suggests an expression cloning strategy for T-cell antigens.
    Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6020-4 PMID: 1378619
  25. T cell receptor antagonist peptides induce positive selection.
    Cell. 1994 Jan 14;76(1):17-27 PMID: 8287475
  26. Tolerance, danger, and the extended family.
    Annu Rev Immunol. 1994;12:991-1045 PMID: 8011301
  27. Constitutive class I-restricted exogenous presentation of self antigens in vivo.
    J Exp Med. 1996 Sep 1;184(3):923-30 PMID: 9064352
  28. Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help.
    J Exp Med. 1997 Jul 7;186(1):65-70 PMID: 9206998
  29. CD8 T cell ignorance or tolerance to islet antigens depends on antigen dose.
    Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12703-7 PMID: 10535986
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20020861
Email
[email protected]
Published
2002-10-21
Pages
1099-104
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2194045
Subset
IM
Corrections
CommentIn
PMID: 12391012
External Links
PubMed source DOI: 10.1084/jem.20020861 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2