Attrition of bystander CD8 T cells during virus-induced T-cell and interferon responses.

Experiments designed to distinguish virus-specific from non-virus-specific T cells showed that bystander T cells underwent apoptosis and substantial attrition in the wake of a strong T-cell response. Memory CD8 T cells (CD8(+) CD44(hi)) were most affected. During acute viral infection, transgenic T cells that were clearly defined as non-virus specific decreased in number and showed an increase in apoptosis.

Bystander sensitization to activation-induced cell death as a mechanism of virus-induced immune suppression.

Viral infections which induce strong T-cell responses are often characterized by a period of transient immunodeficiency associated with the failure of host T cells to proliferate in response to mitogens or to mount memory recall responses to other antigens. During acute infections, most of the activated, proliferating virus-specific T cells are sensitized to undergo apoptosis 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 exposure to their cognate antigen. Using a lymphocytic choriomeningitis virus (LCMV) infection model in which LCMV-immune Thy 1.

Alpha beta and gamma delta T-cell networks and their roles in natural resistance to viral infections.

Both alpha beta and gamma delta T-cell populations and natural killer (NK) cells include cytotoxic, interferon (IFN)-gamma-producing lymphocytes that actively respond to viral infections. We show here that all three populations can provide "natural resistance" to viruses very early in infection and describe how the T-cell populations are modulated to provide this function. gamma delta T cells were shown to play a role in controlling vaccinia virus (VV) infections, as VV grew to much higher titers in gamma delta T-cell knockout mice than in normal mice 3-4 days post-infection.

Minimal bystander activation of CD8 T cells during the virus-induced polyclonal T cell response.

Acute infections with viruses such as lymphocytic choriomeningitis virus (LCMV) are associated with a massive polyclonal T cell response, but the specificities of only a small percentage of these activated T cells are known. To determine if bystander stimulation of T cells not specific to the virus plays a role in this T cell response, we examined two different systems, HY-specific T cell receptor (TCR)-transgenic mice, which have a restricted TCR repertoire, and LCMV-carrier mice, which are tolerant to LCMV. LCMV infection of HY-transgenic C57BL/6 mice induced antiviral CTLs that lysed target cells coated with two of the three immunodominant epitopes previously defined for LCMV (glycoprotein 33 and nucleoprotein 397).