Humphreys, Ian R.  ORCID: https://orcid.org/0000-0002-9512-5337, Loewendorf, Andrea, De Trez, Carl, Schneider, Kirsten, Benedict, Chris A., Munks, Michael W., Ware, Carl F. and Croft, Michael
2007.
OX40 costimulation promotes persistence of cytomegalovirus-specific CD8 T cells: a CD4 dependent mechanism.
Journal of Immunology
179
, pp. 2195-2202.
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Abstract
The mechanisms that regulate CMV-specific T cell responses in vivo are poorly understood. During murine CMV infection of B6 mice, primary responses in the spleen are dominated by CD8 T cells reactive with antigenic epitopes in M45, M57, and m139 murine CMV gene products. However, during the later persistent phase of infection, CD8 T cell responses to epitopes in m139 and M38 viral gene products predominate. The basis for this shift in CD8 T populations is unknown. In this study, we demonstrate that OX40, a TNFR superfamily member, specifically regulates the accumulation of CD8 T cells reactive with the persistent-phase epitopes. Defective CD8 T cell responses in OX40–/– mice were replicated in MHC class II–/– mice implying that CD4 T cells in part controlled the differentiation of the CD8 T cell clones responsive to these epitopes during persistent infection. Furthermore, treatment of infected mice with an agonist OX40 Ab induced expansion of protective primary virus-specific CD8 T cells independent of CD4 T cell help, but CD4 T cells were crucial for anti-OX40 to promote CD8 T cells reactive to the persistent dominant epitopes. Collectively, these results indicate manipulation of OX40 may be useful in improving cellular immunotherapy regimes for treatment of persistent virus infections.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Subjects: | R Medicine > R Medicine (General) |
| ISSN: | 0022-1767 |
| Last Modified: | 17 Oct 2022 08:31 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/350 |
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