E. Flano et al., Requirement for CD4(+) T cells in V beta 4(+)CD8(+) T cell activation associated with latent murine gammaherpesvirus infection, J IMMUNOL, 163(6), 1999, pp. 3403-3408
A CD8(+) T cell lymphocytosis in the peripheral blood is associated with th
e establishment of latency following intranasal infection with murine gamma
herpesvirus-68. Remarkably, a large percentage of the activated CD8(+) T ce
lls of mice expressing different MHC haplotypes express V beta 4(+) TCR, Id
entification of the ligand driving the V beta 4(+)CD8(+) T cell activation
remains elusive, but there is a general correlation between V beta 4(+)CD8(
+) T cell stimulatory activity and establishment of latency in the spleen.
In the current study, the role of CD4(+) T cells in the V beta 4(+)CD8(+) T
cell expansion has been addressed. The results show that CD4(+) T cells ar
e essential for expansion of the V beta 4(+)CD8(+) subset, but not other V
beta subsets, in the peripheral blood. CD4(+) T cells are required relative
ly late in the antiviral response, between 7 and 11 days after infection, a
nd mediate their effect independently of IFN-gamma, Assessment of V beta 4(
+)CD8(+) T cell stimulatory activity using murine gammaherpesvirus-68-speci
fic T cell hybridomas generated from latently infected mice supports the id
ea that CD4(+) T cells control levels of the stimulatory ligand that drives
the V beta 4(+)CD8(+) T cells. As V beta 4(+)CD8(+) T cell expansion also
correlates with levels of activated B cells, these data raise the possibili
ty that CD4(+) T cell-mediated B cell activation is required for optimal ex
pression of the stimulatory ligand. In addition, in cases of low ligand exp
ression, there may also be a direct role for CD4(+) T cell-mediated help fo
r V beta 4(+)CD8(+) T cells.