| First Author | Molloy MJ | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 11 | Pages | 6218-26 |
| PubMed ID | 21531895 | Mgi Jnum | J:173175 |
| Mgi Id | MGI:5013507 | Doi | 10.4049/jimmunol.1003812 |
| Citation | Molloy MJ, et al. (2011) Suppressive CD8+ T Cells Arise in the Absence of CD4 Help and Compromise Control of Persistent Virus. J Immunol 186(11):6218-26 |
| abstractText | There is an urgent need to develop novel therapies for controlling chronic virus infections in immunocompromised patients. Disease associated with persistent gamma-herpesvirus infection (EBV, human herpesvirus 8) is a significant problem in AIDS patients and transplant recipients, and clinical management of these conditions is difficult. Immune surveillance failure followed by gamma-herpesvirus recrudescence can be modeled using murine gamma-herpesvirus (MHV)-68 in mice lacking CD4(+) T cells. In contrast with other chronic infections, no obvious defect in the functional capacity of the viral-specific CD8(+) T cell response was detected. We show in this article that adoptive transfer of MHV-68-specific CD8(+) T cells was ineffective at reducing the viral burden. Together, these indicate the potential presence of T cell extrinsic suppressive factors. Indeed, CD4-depleted mice infected with MHV-68 express increased levels of IL-10, a cytokine capable of suppressing the function of both APCs and T cells. CD4-depleted mice developed a population of CD8(+) T cells capable of producing IL-10 that suppressed viral control. Although exhibiting cell surface markers indicative of activation, the IL-10-producing cells expressed increased levels of programmed death-1 but were not enriched in the MHV-68-specific compartment, nor were they uniformly CD44(hi). Therapeutic administration of an IL-10R blocking Ab enhanced control of the recrudescent virus. These data implicate IL-10 as a promising target for the restoration of immune surveillance against chronic gamma-herpesvirus infection in immunosuppressed individuals. |
