Loss of antiviral cytotoxic T-lymphocyte activity during high-level antigen stimulation

High levels of antigenic stimulation can result in deactivation of CD8⁺ T cells through a variety of mechanisms, including insufficient T-cell help. In the present study, an adoptive transfer system was established in which ovalbumin (OVA)-specific CD8⁺ T cells were transferred to irradiated mice infected with a recombinant vaccinia virus encoding OVA (VV-OVA). Prolonged activation of OVA-specific CD8⁺ T cells resulted in a proliferative block in these cells, although cytotoxic function was maintained. Unlike naive and recently activated OVA-specific T cells, these nonproliferative cytotoxic CD8⁺ T cells did not have antiviral activity following further transfer to mice infected with VV-OVA. Provision of interleukin-2 (IL-2) at the site of virus infection using a recombinant virus encoding antigen and IL-2, as well as the addition of helper T cells, had no effect on the generation of these dysfunctional T cells. Thus, there was no evidence that lack of T-cell help was responsible for CD8⁺ T-cell deactivation in this model.