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Differential impact of CD27 and 4-1BB costimulation on effector and memory CD8 T cell generation following peptide immunization

Differential impact of CD27 and 4-1BB costimulation on effector and memory CD8 T cell generation following peptide immunization
Differential impact of CD27 and 4-1BB costimulation on effector and memory CD8 T cell generation following peptide immunization
The factors that determine differentiation of naive CD8 T cells into memory cells are not well understood. A greater understanding of how memory cells are generated will inform of ways to improve vaccination strategies. In this study, we analyzed the CD8 T cell response elicited by two experimental vaccines comprising a peptide/protein Ag and an agonist that delivers a costimulatory signal via CD27 or 4-1BB. Both agonists increased expansion of Ag-specific CD8 T cells compared with Ag alone. However, their capacity to stimulate differentiation into effector and memory cells differed. CD27 agonists promoted increased expression of perforin and the generation of short-lived memory cells, whereas stimulation with 4-1BB agonists favored generation of stable memory. The memory-promoting effects of 4-1BB were independent of CD4 T cells and were the result of programing within the first 2 d of priming. Consistent with this conclusion, CD27 and 4-1BB–stimulated CD8 T cells expressed disparate amounts of IL-2, IFN-?, CD25, CD71, and Gp49b as early as 3 d after in vivo activation. In addition, memory CD8 T cells, generated through priming with CD27 agonists, proliferated more extensively than did 4-1BB–generated memory cells, but these cells failed to persist. These data demonstrate a previously unanticipated link between the rates of homeostatic proliferation and memory cell attrition. Our study highlights a role for these receptors in skewing CD8 T cell differentiation into effector and memory cells and provides an approach to optimize vaccines that elicit CD8 T cell responses.
0022-1767
244-251
Willoughby, J.E.
aa6969bd-3830-4e1b-83ac-6369b5711e1f
Kerr, J.P.
ad03573b-3f58-4a5d-9cc5-058076285d44
Rogel, A.
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Taraban, V.Y.
f73a6e99-d8a6-4f5e-b1d2-2952ce7627aa
Buchan, S.L.
9ade187d-f127-45de-ad90-9d544d64718a
Johnson, P.W.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Al-Shamkhani, A.
0a40b3ce-9d71-4d41-9369-7212f0a84504
Willoughby, J.E.
aa6969bd-3830-4e1b-83ac-6369b5711e1f
Kerr, J.P.
ad03573b-3f58-4a5d-9cc5-058076285d44
Rogel, A.
5a895ba8-c877-484f-a9c1-34a2b1af6414
Taraban, V.Y.
f73a6e99-d8a6-4f5e-b1d2-2952ce7627aa
Buchan, S.L.
9ade187d-f127-45de-ad90-9d544d64718a
Johnson, P.W.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Al-Shamkhani, A.
0a40b3ce-9d71-4d41-9369-7212f0a84504

Willoughby, J.E., Kerr, J.P., Rogel, A., Taraban, V.Y., Buchan, S.L., Johnson, P.W. and Al-Shamkhani, A. (2014) Differential impact of CD27 and 4-1BB costimulation on effector and memory CD8 T cell generation following peptide immunization. Journal of Immunology, 193 (1), 244-251. (doi:10.4049/jimmunol.1301217). (PMID:24860188)

Record type: Article

Abstract

The factors that determine differentiation of naive CD8 T cells into memory cells are not well understood. A greater understanding of how memory cells are generated will inform of ways to improve vaccination strategies. In this study, we analyzed the CD8 T cell response elicited by two experimental vaccines comprising a peptide/protein Ag and an agonist that delivers a costimulatory signal via CD27 or 4-1BB. Both agonists increased expansion of Ag-specific CD8 T cells compared with Ag alone. However, their capacity to stimulate differentiation into effector and memory cells differed. CD27 agonists promoted increased expression of perforin and the generation of short-lived memory cells, whereas stimulation with 4-1BB agonists favored generation of stable memory. The memory-promoting effects of 4-1BB were independent of CD4 T cells and were the result of programing within the first 2 d of priming. Consistent with this conclusion, CD27 and 4-1BB–stimulated CD8 T cells expressed disparate amounts of IL-2, IFN-?, CD25, CD71, and Gp49b as early as 3 d after in vivo activation. In addition, memory CD8 T cells, generated through priming with CD27 agonists, proliferated more extensively than did 4-1BB–generated memory cells, but these cells failed to persist. These data demonstrate a previously unanticipated link between the rates of homeostatic proliferation and memory cell attrition. Our study highlights a role for these receptors in skewing CD8 T cell differentiation into effector and memory cells and provides an approach to optimize vaccines that elicit CD8 T cell responses.

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More information

Accepted/In Press date: 24 April 2014
e-pub ahead of print date: 23 May 2014
Published date: 1 July 2014
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 390017
URI: http://eprints.soton.ac.uk/id/eprint/390017
ISSN: 0022-1767
PURE UUID: 939ffa57-b042-4cf2-a8d8-0d5c1793b495
ORCID for J.E. Willoughby: ORCID iD orcid.org/0000-0002-6326-4519
ORCID for P.W. Johnson: ORCID iD orcid.org/0000-0003-2306-4974
ORCID for A. Al-Shamkhani: ORCID iD orcid.org/0000-0003-0727-4189

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Date deposited: 17 Mar 2016 11:53
Last modified: 15 Mar 2024 03:31

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Contributors

Author: J.E. Willoughby ORCID iD
Author: J.P. Kerr
Author: A. Rogel
Author: V.Y. Taraban
Author: S.L. Buchan
Author: P.W. Johnson ORCID iD
Author: A. Al-Shamkhani ORCID iD

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