IMMUNOBIOLOGY

Most HIV individuals require lifelong highly active antiretroviral therapy (HAART) to suppress HIV replication, but fail to eliminate the virus in part because of residual replication in gut-associated lymphoid tissues (GALT). Naturally elic-ited HIV-specific CD8 T cells generated in the acute and chronic infectious phases exhibit antiviral activity, but decrease in number after HAART. Therapeutic vac-cines represent a potential strategy to expand cellular responses, although pre-vious efforts have been largely unsuc-cessful, conceivably because of a lack of responding HIV-specific central-memory CD8 T cells (Tcm). To determine whether patients receiving HAART possess CD8 T cells with Tcm qualities that are ame-nable to augmentation, HIV-specific CD8 T-cell clones were derived from HIV-reactive CD28CD8 T-cell lines isolated from 7 HIV HAART-treated patients, ex-panded ex vivo, and reinfused into their autologous host. Tracking of the cells in vivo revealed that clones could persist for> 84 days, maintain expression and/or re-express CD28, up-regulate CD62L, secrete IL-2, proliferate on cognate Ag encounter and localize to the rectal mu-cosa. These results suggest some in-fused cells exhibited phenotypic and func-tional characteristics shared with Tcm in vivo, and imply that more effective thera-peutic vaccination strategies targeting CD8 Tcm in patients on HAART might provide hosts with expanded, long-lasting immune responses not only sys-temically but also in GALT. This study is registered at www.clinicaltrials.gov a