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 mic e infected with a recombinant vaccinia virus encoding OVA (VV-OVA), Prolong ed activation of OVA-specific CD8(+) T cells resulted in a proliferative bl ock in these cells, although cytotoxic function was maintained. Unlike naiv e and recently activated OVA-specific T cells, these nonproliferative cytot oxic CD8(+) T cells did not have antiviral activity following further trans fer 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 generatio n 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.