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Cellular immune response - bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

Cellular immune response - bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid
Cellular immune response - bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid
Antigen-specific CD4+ T cells are central to natural and vaccine-induced immunity. However an ongoing antigen-specific T-cell response can influence surrounding T cells with unrelated antigen specificities. We previously observed this bystander effect in healthy human subjects following recall vaccination with tetanus toxoid (TT). Since this interplay could be important for maintenance of memory, we have moved to a mouse model for further analysis. We investigated if boosting memory CD4+ T cells against TT in vivo would influence injected CD4+ TCR transgenic T cells (OT-II) specific for an unrelated ovalbumin (OVA) peptide (OVAp). We found that, if OT-II cells were pre-activated with OVAp in vitro,they showed a bystander proliferative response during the ongoing parallel TT-specific response. Bystander proliferation was dependent on boosting of the TT-specific memory response in the recipients, with no effect in naïve mice. Bystander stimulation was also proportional to the strength of the TT-specific memory T-cell response. T cells activated in vitro displayed functional receptors for IL-2 and IL-7, suggesting these as potential mediators. This cross-talk between a stimulated CD4+ memory T-cell response and CD4+ T cells activated by an unrelated antigen could be important in human subjects continually buffeted by environmental antigens
bystander activation, CD4+ T cells, vaccination, T cell memory
0014-2980
976-985
Di Genova, Gianfranco
c3b15017-39f0-4d9d-8b55-bb1da7358468
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Suchacki, Amy
23de61f4-fe22-4a69-8747-68c8c03e99a8
Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Di Genova, Gianfranco
c3b15017-39f0-4d9d-8b55-bb1da7358468
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Suchacki, Amy
23de61f4-fe22-4a69-8747-68c8c03e99a8
Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c

Di Genova, Gianfranco, Savelyeva, Natalia, Suchacki, Amy, Thirdborough, Stephen M. and Stevenson, Freda K. (2010) Cellular immune response - bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid. European Journal of Immunology, 40 (4), 976-985. (doi:10.1002/eji.200940017). (PMID:20104490)

Record type: Article

Abstract

Antigen-specific CD4+ T cells are central to natural and vaccine-induced immunity. However an ongoing antigen-specific T-cell response can influence surrounding T cells with unrelated antigen specificities. We previously observed this bystander effect in healthy human subjects following recall vaccination with tetanus toxoid (TT). Since this interplay could be important for maintenance of memory, we have moved to a mouse model for further analysis. We investigated if boosting memory CD4+ T cells against TT in vivo would influence injected CD4+ TCR transgenic T cells (OT-II) specific for an unrelated ovalbumin (OVA) peptide (OVAp). We found that, if OT-II cells were pre-activated with OVAp in vitro,they showed a bystander proliferative response during the ongoing parallel TT-specific response. Bystander proliferation was dependent on boosting of the TT-specific memory response in the recipients, with no effect in naïve mice. Bystander stimulation was also proportional to the strength of the TT-specific memory T-cell response. T cells activated in vitro displayed functional receptors for IL-2 and IL-7, suggesting these as potential mediators. This cross-talk between a stimulated CD4+ memory T-cell response and CD4+ T cells activated by an unrelated antigen could be important in human subjects continually buffeted by environmental antigens

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More information

Published date: 26 January 2010
Keywords: bystander activation, CD4+ T cells, vaccination, T cell memory
Organisations: Faculty of Medicine, Cancer Sciences

Identifiers

Local EPrints ID: 73617
URI: http://eprints.soton.ac.uk/id/eprint/73617
ISSN: 0014-2980
PURE UUID: 681c23f8-34a6-4009-a25e-2ca3cf596b6c
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

Catalogue record

Date deposited: 10 Mar 2010
Last modified: 24 Sep 2019 00:54

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Contributors

Author: Gianfranco Di Genova
Author: Amy Suchacki

University divisions

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