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.
Rolph
M S
MS
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Canberra, Australia.
Matthaei
K I
KI
Carbone
F R
FR
Heath
W R
WR
Ramshaw
I A
IA
D000818:Animals; D000941:Antigens / Q000276:immunology; D002455:Cell Division; D005822:Genetic Vectors / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology / Q000502:physiology; D014779:Virus Replication
D000941:Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma; D010047:Ovalbumin