Studies on feline CD8+ T cell non-cytolytic anti-feline immunodeficiency virus (FIV) activity

CD8(+) T cells in FIV-infected cats inhibit feline immunodeficiency virus (FIV) replication by producing a soluble factor(s). In the present study, four SPF cats were experiment-ally infected with FIV. The period during which the anti-FIV activity of CD8(+) T cells became detectable was investigated, and the presence or absence of this activity in the lymph nodes and spleen was examined. Furthermore, we investigated which step(s) of the FIV replication cycle are affected by this antiviral activity. This antiviral activity became detectable five weeks after FIV infection in early cases, and it was simultaneous with or one week after the induction of humoral immunity. All cats having CD8(+) T cells with anti-FIV activity in the peripheral blood also possessed CD8(+) T cells with anti-FIV activity in the lymph nodes. In contrast, CD8(+) T cells from the spleens of some, but not all cats showed anti-FIV activity. CD8(+) T cell-depleted peripheral blood mononuclear cells were cultured and reconstituted with CD8(+) T cells on day 12 of culture after confirming FIV replication. The number of FIV proviral DNA copies in the cells did not change, but the amount of FIV p24 antigen production in the culture supernatant and the number of FIV mRNA copies in the cells decreased. These findings suggested that CD8(+) T cell anti-FIV activity acts at the level of FIV mRNA synthesis from the FIV proviral DNA, inhibiting FIV replication by a non-cytolytic mechanism.