Killing Kinetics of Simian Immunodeficiency Virus-Specific

Both the magnitude and function of vaccine-induced HIV-specific CD8 CTLs are likely to be important in the outcome of infection. We hypothesized that rapid cytolysis by CTLs may facilitate control of viral challenge. Release kinetics of the cytolytic effector molecules granzyme B and perforin, as well as the expression of the degranulation marker CD107a and IFN- were simultaneously studied in SIV Gag164–172 KP9-specific CD8 T cells from Mane-A*10 pigtail macaques. Macaques were vac-cinated with either prime-boost poxvirus vector vaccines or live-attenuated SIV vaccines. Prime-boost vaccination induced Gag-specific CTLs capable of only slow (after 3 h) production of IFN- and with limited (<5%) degranulation and granzyme B release. Vaccination with live-attenuated SIV resulted in a rapid cytolytic profile of SIV-specific CTLs with rapid (<0.5 h) and robust (>50 % of tetramer-positive CD8 T cells) degranulation and granzyme B release. The cytolytic phenotype following live-atten-uated SIV vaccinations were similar to that associated with the partial resolution of viremia following SIVmac251 challenge of prime-boost-vaccinated macaques, albeit with less IFN- expression. High proportions of KP9-specific T cells expressed the costimulatory molecule CD28 when they exhibited a rapid cytolytic phenotype. The delayed cytolytic phenotype exhibited by standard vector-based vaccine-induced CTLs may limit the ability of T cell-based HIV vaccines to rapidly control acute infection following a pathogenic lentiviral exposure. The Journal of Immunology, 2007, 179: 4571–4579. R esearch shows that CD8 T cells help partially controlHIV-1 infection in humans and SIV infection in ma-caques. Depletion of CD8 T cells results in a brisk rise in viremia in SIV-infected macaques (1–5). Considerabl