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Induction of a type 1 regulatory CD4 T cell response following Vβ8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis

Induction of a type 1 regulatory CD4 T cell response following Vβ8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis
Induction of a type 1 regulatory CD4 T cell response following Vβ8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis

DNA vaccination has been used to generate effective cellular as well as humoral immunity against target antigens. Here we have investigated the induction and involvement of regulatory T cell (Treg) responses in mediating prevention of experimental autoimmune encephalomyelitis (EAE), following vaccination with plasmid DNA encoding the TCR Vβ8.2 chain predominantly displayed on disease-causing lymphocytes. Vaccination with DNA encoding the wild-type TCR results in priming of type 1 CD4 Treg and skewing of the global response to myelin basic protein in a Th2 direction, leading to significant protection from disease. In contrast, vaccination with mutant DNA encoding altered residues critically involved in recognition by the Treg results in priming of a type 2 regulatory response which fails to mediate immune deviation or protection from EAE. Control mice immunized with DNA, encoding TCR with changes at an irrelevant site, were protected from antigen-induced disease. Furthermore, protection can be transferred into naive recipients with CD4 Treg from wild-type DNA-immunized mice but not from animals vaccinated with the mutant DNA. These data suggest that vaccination with plasmid DNA encoding one or multiple Vβ genes can be exploited to enhance natural regulatory responses for intervention in autoimmune conditions.

DNA vaccine, Experimental autoimmune encephalomyelitis, Regulatory T cells, T1/T2, TCR
0953-8178
835-841
Kumar, Vipin
492e5247-f499-42a8-80ec-b5ed3487a7c2
Maglione, Jeannie
2260333f-c058-48d4-a1ff-7bc2c505e8af
Thatte, Jayant
10361447-4b16-4092-9bb7-e82759ab0097
Pederson, Brian
29ceb3bc-2fc6-43e0-b2d0-f4f481b96b28
Sercarz, Eli
614be174-8001-4b60-98b7-fe62a70fa7ac
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Kumar, Vipin
492e5247-f499-42a8-80ec-b5ed3487a7c2
Maglione, Jeannie
2260333f-c058-48d4-a1ff-7bc2c505e8af
Thatte, Jayant
10361447-4b16-4092-9bb7-e82759ab0097
Pederson, Brian
29ceb3bc-2fc6-43e0-b2d0-f4f481b96b28
Sercarz, Eli
614be174-8001-4b60-98b7-fe62a70fa7ac
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc

Kumar, Vipin, Maglione, Jeannie, Thatte, Jayant, Pederson, Brian, Sercarz, Eli and Ward, E. Sally (2001) Induction of a type 1 regulatory CD4 T cell response following Vβ8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis. International Immunology, 13 (6), 835-841. (doi:10.1093/intimm/13.6.835).

Record type: Article

Abstract

DNA vaccination has been used to generate effective cellular as well as humoral immunity against target antigens. Here we have investigated the induction and involvement of regulatory T cell (Treg) responses in mediating prevention of experimental autoimmune encephalomyelitis (EAE), following vaccination with plasmid DNA encoding the TCR Vβ8.2 chain predominantly displayed on disease-causing lymphocytes. Vaccination with DNA encoding the wild-type TCR results in priming of type 1 CD4 Treg and skewing of the global response to myelin basic protein in a Th2 direction, leading to significant protection from disease. In contrast, vaccination with mutant DNA encoding altered residues critically involved in recognition by the Treg results in priming of a type 2 regulatory response which fails to mediate immune deviation or protection from EAE. Control mice immunized with DNA, encoding TCR with changes at an irrelevant site, were protected from antigen-induced disease. Furthermore, protection can be transferred into naive recipients with CD4 Treg from wild-type DNA-immunized mice but not from animals vaccinated with the mutant DNA. These data suggest that vaccination with plasmid DNA encoding one or multiple Vβ genes can be exploited to enhance natural regulatory responses for intervention in autoimmune conditions.

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More information

Published date: June 2001
Keywords: DNA vaccine, Experimental autoimmune encephalomyelitis, Regulatory T cells, T1/T2, TCR

Identifiers

Local EPrints ID: 425137
URI: http://eprints.soton.ac.uk/id/eprint/425137
ISSN: 0953-8178
PURE UUID: d34eb7ec-04d7-4db3-ad18-075160124274
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

Catalogue record

Date deposited: 11 Oct 2018 16:30
Last modified: 07 Oct 2020 02:22

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Contributors

Author: Vipin Kumar
Author: Jeannie Maglione
Author: Jayant Thatte
Author: Brian Pederson
Author: Eli Sercarz
Author: E. Sally Ward ORCID iD

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