CD4 T cell control of acute and latent murine gammaherpesvirus infection requires IFNγ

• Published in: Virology (New York, N.Y.) N.Y.), 2005-08, Vol.338 (2), p.201-208
• Main Authors: Sparks-Thissen, Rebecca L., Braaten, Douglas C., Hildner, Kai, Murphy, Theresa L., Murphy, Kenneth M., Virgin, Herbert W.
• Format: Article
• Language: English
• Subjects: CD4 T cell; gammaherpesvirus; Herpesvirus latency; IFNγ; TH1 T cell
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2005.05.011

Murine gammaherpesvirus 68 (γHV68, MHV-68)-specific CD4 T cells control γHV68 infection by reducing the frequency of latently infected cells and by inhibiting viral replication. We have previously demonstrated that CD4 T cells do not require CD8 T or B cells to control γHV68 replication, demonstrating a helper-independent activity of CD4 T cells during γHV68 infection. The effector mechanism(s) required for this helper-independent function of CD4 T cells and for the inhibition of the establishment of latency by CD4 T cells are not known. Since IFNγ has been previously shown to be important for control of acute, latent, and persistent γHV68 infection, we tested the hypothesis that CD4 T cells require IFNγ to limit γHV68 latency and replication. We utilized a previously described system in which T cell receptor (TCR) transgenic T cells (DO.11.10) and a recombinant virus (γHV68.OVA) allow for evaluation of high numbers of virus-specific CD4 T cells during both acute and latent infection. We show here that virus-specific CD4 T cells require IFNγ for their anti-viral function in both acute and latent γHV68 infection. We additionally show that an in vitro derived T helper type 1 (TH1) CD4 T cell clone, which produces IFNγ, inhibits γHV68 replication after adoptive transfer into RAG mice. Together, data presented here demonstrate that both CD4 T cell-mediated helper-independent control of γHV68 replication and inhibition of the establishment of γHV68 latency require IFNγ.