Cc. Zarozinski et al., Bystander sensitization to activation-induced cell death as a mechanism ofvirus-induced immune suppression, J VIROLOGY, 74(8), 2000, pp. 3650-3658
Viral infections which induce strong T-cell responses are often characteriz
ed by a period of transient immunodeficiency associated with the failure of
host T cells to proliferate in response to mitogens or to mount memory rec
all responses to other antigens. During acute infections, most of the activ
ated, proliferating virus-specific T cells are sensitized to undergo apopto
sis on strong T-cell receptor (TCR) stimulation, but it has not been known
why memory T cells not specific for the virus fail to proliferate on exposu
re to their cognate antigen. Using a lymphocytic choriomeningitis virus (LC
MV) infection model in which LCMV-immune Thy 1.1(+) splenocytes are adoptiv
ely transferred into Thy 1.2(+) LCMV carrier mice, we demonstrate here that
T cells clearly defined as not specific for the virus are sensitized to un
dergo activation-induced cell death on TCR stimulation in vitro. This bysta
nder sensitization was in part dependent on the expression of Fas ligand (F
asL) on the activated virus-specific cells and gamma interferon (IFN-gamma)
receptor expression on the bystander T cells. We propose that Fast from hi
ghly activated antiviral T cells may sensitize IFN-gamma-conditioned T cell
s not specific for the virus to undergo apoptosis rather than to proliferat
e on encountering antigen. This may In part explain the failure of memory T
cells to respond to recall antigens during acute and persistent viral infe
ctions.