AIDS is the end result of a prolonged dynamic war of attrition between virus and host, marked by prodigious rates of viral replication opposed by host immune responses and remarkable rates of T cell regeneration (1, 2). Understanding the ultimate failure of the host immune responses to control HIV replication remains one of the central challenges of HIV research. This commentary will focus on efforts to understand why the host cytotoxic T lymphocyte (CTL) response, normally a potent effector response against viral infections, is unable to contain AIDS virus replication.
Most HIV-infected people develop a strong and broadly directed CTL response against HIV (3). This CTL response, which is mediated largely by classical CD8+, MHC class I–restricted lymphocytes, can often be detected without in vitro stimulation, indicating a high frequency of circulating activated effector cells (4). Direct evidence for a...
