Requirement for CD4+ T Cells in Vβ4+CD8+ T Cell Activation Associated with Latent Murine Gammaherpesvirus Infection

Abstract

AbstractA CD8+ T cell lymphocytosis in the peripheral blood is associated with the establishment of latency following intranasal infection with murine gammaherpesvirus-68. Remarkably, a large percentage of the activated CD8+ T cells of mice expressing different MHC haplotypes express Vβ4+ TCR. Identification of the ligand driving the Vβ4+CD8+ T cell activation remains elusive, but there is a general correlation between Vβ4+CD8+ T cell stimulatory activity and establishment of latency in the spleen. In the current study, the role of CD4+ T cells in the Vβ4+CD8+ T cell expansion has been addressed. The results show that CD4+ T cells are essential for expansion of the Vβ4+CD8+ subset, but not other Vβ subsets, in the peripheral blood. CD4+ T cells are required relatively late in the antiviral response, between 7 and 11 days after infection, and mediate their effect independently of IFN-γ. Assessment of Vβ4+CD8+ T cell stimulatory activity using murine gammaherpesvirus-68-specific T cell hybridomas generated from latently infected mice supports the idea that CD4+ T cells control levels of the stimulatory ligand that drives the Vβ4+CD8+ T cells. As Vβ4+CD8+ T cell expansion also correlates with levels of activated B cells, these data raise the possibility that CD4+ T cell-mediated B cell activation is required for optimal expression of the stimulatory ligand. In addition, in cases of low ligand expression, there may also be a direct role for CD4+ T cell-mediated help for Vβ4+CD8+ T cells.