Journal
JOURNAL OF IMMUNOLOGY
Volume 179, Issue 4, Pages 2195-2202Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.4.2195
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Funding
- NCI NIH HHS [CA91837] Funding Source: Medline
- NIAID NIH HHS [AI67341, AI048073, AI057840, R37AI33068] Funding Source: Medline
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The mechanisms that regulate CMV-specific T cell responses in vivo are poorly understood. During murine CMV infection of 136 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.
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