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

Murine Laninialierpesvirus 68 (gamma HV68, MHV-68)-specific CD4 T cells control -yHV68 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 gamma HV68 replication, demonstrating a helper-independent activity of CD4 T cells during gamma HV68 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 IFN gamma has been previously shown to be important for control of acute, latent, and persistent -yHV68 infection, we tested the hypothesis that CD4 T cells require IFN gamma to limit gamma HV68 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 (gamma HV68.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 IFN gamma for their anti-viral function in both acute and latent gamma HV68 infection. We additionally show that an in vitro derived T helper type 1 (TH 1) CD4 T cell clone, which produces IFN gamma, inhibits gamma HV68 replication after adoptive transfer into RAG mice. Together, data presented here demonstrate that both CD4 T cel-mediated helper-independent control of gamma HV68 replication and inhibition of the establishment of gamma HV68 latency require IFN gamma. (c) 2005 Elsevier Inc. All rights reserved.