title: CD4 T cell control of acute and latent murine gammaherpesvirus infection requires IFNgamma.
abstract: Murine gammaherpesvirus 68 (gammaHV68, MHV-68)-specific CD4 T cells control gammaHV68 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 gammaHV68 replication, demonstrating a helper-independent activity of CD4 T cells during gammaHV68 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 IFNgamma has been previously shown to be important for control of acute, latent, and persistent gammaHV68 infection, we tested the hypothesis that CD4 T cells require IFNgamma to limit gammaHV68 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 (gammaHV68.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 IFNgamma for their anti-viral function in both acute and latent gammaHV68 infection. We additionally show that an in vitro derived T helper type 1 (TH1) CD4 T cell clone, which produces IFNgamma, inhibits gammaHV68 replication after adoptive transfer into RAG mice. Together, data presented here demonstrate that both CD4 T cell-mediated helper-independent control of gammaHV68 replication and inhibition of the establishment of gammaHV68 latency require IFNgamma.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Ave., Box 8118, St. Louis, MO 63110, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Sparks-Thissen
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Braaten
authors.forename: Kai
authors.initials: K
authors.lastname: Hildner
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D018142:Gammaherpesvirinae / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D007371:Interferon-gamma / Q000627:therapeutic use*; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D017735:Virus Latency / Q000276:immunology
chemical_list: D007371:Interferon-gamma