EVIDENCE FOR RAPID DISAPPEARANCE OF INITIALLY EXPANDED HIV-SPECIFIC CD8(-CELL CLONES DURING PRIMARY HIV-INFECTION() T)

Down-regulation of the initial burst of viremia during primary HIV inf ection is thought to be mediated predominantly by HIV-specific cytotox ic T lymphocytes, and the appearance of this response is associated wi th major perturbations of the T cell receptor repertoire. Changes in t he T cell receptor repertoire of virus-specific cytotoxic T lymphocyte s were analyzed in patients with primary infection to understand the f ailure of the cellular immune response to control viral spread and rep lication. This analysis demonstrated that a significant number of HIV- specific T cell clones involved in the primary immune response rapidly disappeared. The disappearance was not the result of mutations in the virus epitopes recognized by these clones. Evidence is provided that phenomena such as high-dose tolerance or clonal exhaustion might be in volved in the disappearance of these monoclonally expanded HIV-specifi c cytotoxic T cell clones, These findings should provide insights into how HIV, and possibly other viruses, elude the host immune response d uring primary infection.