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PMID: 11560988 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Phenotypic and functional analysis of CD8(+) T cells undergoing peripheral deletion in response to cross-presentation of self-antigen.

The Journal of experimental medicine ·Vol. 194 ·No. 6 ·2001-09-17 ·Pages 707-17

Hernandez J, Aung S, Redmond WL, Sherman LA

Abstract

Not all T cells specific for autoantigens are eliminated in the thymus, and therefore alternate mechanisms are required to prevent potentially autoreactive T cells from developing into effectors. Adoptive transfer of CD8(+) T cells from influenza hemagglutinin-specific Clone 4 TCR transgenic mice into mice that express hemagluttinin in the pancreatic islets results in tolerance. This is preceded by activation of Clone 4 T cells that encounter antigen cross-presented in the draining lymph nodes of the pancreas. In this report we compare the phenotype, function, and costimulatory requirements of Clone 4 T cells activated by endogenous self-antigen, with Clone 4 T cells stimulated by influenza virus. The cells undergoing tolerance upregulate both CD69 and CD44, yet only partially downregulate CD62L, and do not express CD49d or CD25. Most importantly, they lack the ability to produce interferon-gamma in response to antigen and show no cytolytic activity. Clone 4 T cells disappear after several cycles of division, apparently without leaving the site of initial activation. Surprisingly, despite the fact that such stimulation occurs through recognition of antigen that is cross-presented by a professional antigen-presenting cell, we find this activation is not dependent on costimulation through CD28. These data demonstrate that the recognition by naive CD8(+) T cells of cross-presented self-antigen results in localized proliferation and deletion, without the production of effector cells.

MeSH Terms
Animals Antigen Presentation/immunology Antigens, CD/immunology Autoantigens/immunology B7-1 Antigen/immunology B7-2 Antigen CD8-Positive T-Lymphocytes/cytology,immunology Cell Differentiation Cell Division Clonal Deletion Cross Reactions Immunophenotyping Lymph Nodes/immunology Membrane Glycoproteins/immunology Mice Mice, Inbred BALB C Pancreas/immunology
Chemicals
Antigens, CD Autoantigens B7-1 Antigen B7-2 Antigen Cd86 protein, mouse Membrane Glycoproteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hernandez J
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Aung S
Redmond W L
Sherman L A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.194.6.707
Published
2001-09-17
Pages
707-17
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2195957
Subset
IM
Grants
NCI NIH HHS · CA57855 · United States
NIDDK NIH HHS · DK50824 · United States
External Links
PubMed source DOI: 10.1084/jem.194.6.707 PMC Full Text View journal details
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