ACCUMULATION OF HUMAN IMMUNODEFICIENCY VIRUS-SPECIFIC CYTOTOXIC T-LYMPHOCYTES AWAY FROM THE PREDOMINANT SITE OF VIRUS-REPLICATION DURING PRIMARY INFECTION

Down-regulation of the initial burst of viremia during primary human i mmuno-deficiency virus (HIV) infection is thought to be mediated predo minantly by HIV-specific CD8(+) cytotoxic T lymphocytes (CTL). This re sponse is associated with major perturbations in the T cell receptor ( TCR) repertoire. To investigate the failure of the cellular immune res ponse to adequately control viral spread and replication and to preven t establishment of HIV infection, changes in the TCR repertoire and in the distribution of virus-specific CTL between blood and lymph node w ere analyzed in three patients with primary infection. By the combined use of clonotype-specific polymerase chain reaction and analysis of t he frequency of in vivo activated HIV-specific CTL, it was shown that HIV-specific CTL clones preferentially accumulated in blood as opposed to lymph node. Accumulation of HIV-specific CTL in blood occurred pri or to effective downregulation of virus replication in both blood and lymph node. These findings should provide new insights into how HIV, a nd possibly other viruses, elude the immune response of the host durin g primary infection.