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OX40 costimulation promotes persistence of cytomegalovirus-specific CD8 T cells: a CD4 dependent mechanism

Humphreys, Ian R. ORCID:, 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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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: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
ISSN: 0022-1767
Last Modified: 17 Oct 2022 08:31

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