par Humphreys, Ian R.;Loewendorf, Andrea;De Trez, Carl 
;Schneider, Kirsten;Benedict, Chris A.;Munks, Michael W.;Ware, Carl F.;Croft, Michael
Référence The Journal of immunology, 179, 4, page (2195-2202)
Publication Publié, 2007
;Schneider, Kirsten;Benedict, Chris A.;Munks, Michael W.;Ware, Carl F.;Croft, MichaelRéférence The Journal of immunology, 179, 4, page (2195-2202)
Publication Publié, 2007
Article révisé par les pairs
| Résumé : | 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. |
