Vaccination expands antigen-specific cd4+ memory T cells and mobilizes bystander central memory T cells
Vaccination expands antigen-specific cd4+ memory T cells and mobilizes bystander central memory T cells
CD4+ T helper memory (Thmem) cells influence both natural and vaccine-boosted immunity, but mechanisms for their maintenance remain unclear. Pro-survival signals from the common gamma-chain cytokines, in particular IL-7, appear important. Previously we showed in healthy volunteers that a booster vaccination with tetanus toxoid (TT) expanded peripheral blood TT-specific Thmem cells as expected, but was accompanied by parallel increase of Thmem cells specific for two unrelated and non cross-reactive common recall antigens. Here, in a new cohort of healthy human subjects, we compare blood vaccine-specific and bystander Thmem cells in terms of differentiation stage, function, activation and proliferative status. Both responses peaked 1 week post-vaccination. Vaccine-specific cytokine-producing Thmem cells were predominantly effector memory, whereas bystander cells were mainly of central memory phenotype. Importantly, TT-specific Thmem cells were activated (CD38High HLA-DR+), cycling or recently divided (Ki-67+), and apparently vulnerable to death (IL-7R?Low and Bcl-2 Low). In contrast, bystander Thmem cells were resting (CD38Low HLA-DR- Ki-67-) with high expression of IL-7R? and Bcl-2. These findings allow a clear distinction between vaccine-specific and bystander Thmem cells, suggesting the latter do not derive from recent proliferation but from cells mobilized from as yet undefined reservoirs. Furthermore, they reveal the interdependent dynamics of specific and bystander T-cell responses which will inform assessments of responses to vaccines.
1-19
Li Causi, Eleonora
edaea0b4-0aa2-431c-8a36-863b0e26df4e
Parikh, Suraj C.
73ab5819-e20f-4b69-b49c-95a9debc9f2b
Chudley, Lindsey
ec25c30c-369d-4516-b872-4cb3c135c10a
Layfield, David
3f5ffdd6-6ec0-43dd-95a8-5752bcefe7f5
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Di Genova, Gianfranco
c3b15017-39f0-4d9d-8b55-bb1da7358468
2 September 2015
Li Causi, Eleonora
edaea0b4-0aa2-431c-8a36-863b0e26df4e
Parikh, Suraj C.
73ab5819-e20f-4b69-b49c-95a9debc9f2b
Chudley, Lindsey
ec25c30c-369d-4516-b872-4cb3c135c10a
Layfield, David
3f5ffdd6-6ec0-43dd-95a8-5752bcefe7f5
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Di Genova, Gianfranco
c3b15017-39f0-4d9d-8b55-bb1da7358468
Li Causi, Eleonora, Parikh, Suraj C., Chudley, Lindsey, Layfield, David, Ottensmeier, Christian H., Stevenson, Freda K. and Di Genova, Gianfranco
(2015)
Vaccination expands antigen-specific cd4+ memory T cells and mobilizes bystander central memory T cells.
PLoS ONE, 10 (9), .
(doi:10.1371/journal.pone.0136717).
(PMID:26332995)
Abstract
CD4+ T helper memory (Thmem) cells influence both natural and vaccine-boosted immunity, but mechanisms for their maintenance remain unclear. Pro-survival signals from the common gamma-chain cytokines, in particular IL-7, appear important. Previously we showed in healthy volunteers that a booster vaccination with tetanus toxoid (TT) expanded peripheral blood TT-specific Thmem cells as expected, but was accompanied by parallel increase of Thmem cells specific for two unrelated and non cross-reactive common recall antigens. Here, in a new cohort of healthy human subjects, we compare blood vaccine-specific and bystander Thmem cells in terms of differentiation stage, function, activation and proliferative status. Both responses peaked 1 week post-vaccination. Vaccine-specific cytokine-producing Thmem cells were predominantly effector memory, whereas bystander cells were mainly of central memory phenotype. Importantly, TT-specific Thmem cells were activated (CD38High HLA-DR+), cycling or recently divided (Ki-67+), and apparently vulnerable to death (IL-7R?Low and Bcl-2 Low). In contrast, bystander Thmem cells were resting (CD38Low HLA-DR- Ki-67-) with high expression of IL-7R? and Bcl-2. These findings allow a clear distinction between vaccine-specific and bystander Thmem cells, suggesting the latter do not derive from recent proliferation but from cells mobilized from as yet undefined reservoirs. Furthermore, they reveal the interdependent dynamics of specific and bystander T-cell responses which will inform assessments of responses to vaccines.
Other
journal.pone.0136717.PDF
- Version of Record
More information
Accepted/In Press date: 7 August 2015
Published date: 2 September 2015
Organisations:
Cancer Sciences
Identifiers
Local EPrints ID: 396336
URI: http://eprints.soton.ac.uk/id/eprint/396336
ISSN: 1932-6203
PURE UUID: 85ff4426-d7f5-4a6e-8c0a-57d561a4a8de
Catalogue record
Date deposited: 08 Jun 2016 10:52
Last modified: 15 Mar 2024 02:53
Export record
Altmetrics
Contributors
Author:
Eleonora Li Causi
Author:
Suraj C. Parikh
Author:
Lindsey Chudley
Author:
David Layfield
Author:
Gianfranco Di Genova
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics