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Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor immune responses

Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor immune responses
Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor immune responses
his study addresses the relative importance of CD134 (OX40) and CD137 (4-1BB) in the costimulation of CD4+ and CD8+ T cells under comparable conditions of antigenic stimulation. We demonstrate that CD134 is capable of directly costimulating CD8+ T cells. However, costimulation of CD8+ T cells by CD134 is less potent than that triggered by CD137. The higher costimulatory activity of CD137, when compared with CD134, correlates well with its faster expression kinetics and higher levels on CD8+ T cells. Furthermore, induction of CD137 expression on CD8+ T cells is highly sensitive to low levels of TCR stimulation, which is in contrast with CD134. Conversely, CD134 is more effective than CD137 in costimulating CD4+ T cells. This, however, could not be attributed to differential expression. We also demonstrate that the transient nature of CD134 and CD137 expression on activated CD4+ T cells is the resultof proteolytic shedding. Consistent with the greater ability of CD137 to costimulate CD8+ T cells, stimulation of CD137 in vivo is considerably more effective than CD134 in augmenting anti-tumor immune responses. Therefore, agents that stimulate signaling via CD137 are likely to be more useful in clinical conditions where highly effective CD8+ CTL responses are required.
T cell activation, costimulation, tumor immunity, immunotherapy
0014-2980
3617-3627
Taraban, Vadim Y.
d709dcbb-ff36-4514-85da-08ca68aafcd3
Rowley, Tania F.
3a29866f-3e2c-4ee8-8fe6-fd189ac1eb3d
O'Brien, Lyn
0dea42f9-e160-4929-80db-35001165c280
Chan, H.T. Claude
b109c93f-7e9a-44ee-ad12-da757b1b11fc
Haswell, Linsey E.
7e2a20d5-8dda-42dd-a956-962ce5446337
Green, Michael H.A
8de50746-ff9d-48eb-a2b0-aa687c211644
Tutt, Alison L.
46ce577b-aea1-412d-84ea-fc4dab794469
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Taraban, Vadim Y.
d709dcbb-ff36-4514-85da-08ca68aafcd3
Rowley, Tania F.
3a29866f-3e2c-4ee8-8fe6-fd189ac1eb3d
O'Brien, Lyn
0dea42f9-e160-4929-80db-35001165c280
Chan, H.T. Claude
b109c93f-7e9a-44ee-ad12-da757b1b11fc
Haswell, Linsey E.
7e2a20d5-8dda-42dd-a956-962ce5446337
Green, Michael H.A
8de50746-ff9d-48eb-a2b0-aa687c211644
Tutt, Alison L.
46ce577b-aea1-412d-84ea-fc4dab794469
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504

Taraban, Vadim Y., Rowley, Tania F., O'Brien, Lyn, Chan, H.T. Claude, Haswell, Linsey E., Green, Michael H.A, Tutt, Alison L., Glennie, Martin J. and Al-Shamkhani, Aymen (2002) Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor immune responses. European Journal of Immunology, 32 (12), 3617-3627. (doi:10.1002/1521-4141(200212)32:12<3617::AID-IMMU3617>3.0.CO;2-M).

Record type: Article

Abstract

his study addresses the relative importance of CD134 (OX40) and CD137 (4-1BB) in the costimulation of CD4+ and CD8+ T cells under comparable conditions of antigenic stimulation. We demonstrate that CD134 is capable of directly costimulating CD8+ T cells. However, costimulation of CD8+ T cells by CD134 is less potent than that triggered by CD137. The higher costimulatory activity of CD137, when compared with CD134, correlates well with its faster expression kinetics and higher levels on CD8+ T cells. Furthermore, induction of CD137 expression on CD8+ T cells is highly sensitive to low levels of TCR stimulation, which is in contrast with CD134. Conversely, CD134 is more effective than CD137 in costimulating CD4+ T cells. This, however, could not be attributed to differential expression. We also demonstrate that the transient nature of CD134 and CD137 expression on activated CD4+ T cells is the resultof proteolytic shedding. Consistent with the greater ability of CD137 to costimulate CD8+ T cells, stimulation of CD137 in vivo is considerably more effective than CD134 in augmenting anti-tumor immune responses. Therefore, agents that stimulate signaling via CD137 are likely to be more useful in clinical conditions where highly effective CD8+ CTL responses are required.

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Published date: 2002
Keywords: T cell activation, costimulation, tumor immunity, immunotherapy

Identifiers

Local EPrints ID: 26632
URI: http://eprints.soton.ac.uk/id/eprint/26632
ISSN: 0014-2980
PURE UUID: 33e47258-a028-4e23-b181-cfaf132ee415
ORCID for Aymen Al-Shamkhani: ORCID iD orcid.org/0000-0003-0727-4189

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Date deposited: 21 Apr 2006
Last modified: 03 Dec 2019 01:56

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Contributors

Author: Vadim Y. Taraban
Author: Tania F. Rowley
Author: Lyn O'Brien
Author: H.T. Claude Chan
Author: Linsey E. Haswell
Author: Michael H.A Green
Author: Alison L. Tutt

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