Kinetics of virus-specific CD8+ T cells and the control of human immunodeficiency virus infection

Abstract

Several primate models indicate that cytotoxic T lymphocyte-inducing vaccines may be unable to prevent human immunodeficiency virus infection but may have a long-term benefit in controlling viral replication and delaying disease progression. Here we show that analysis of the kinetics of antigen-specific CD8+ T-cell expansion suggests a delay in activation following infection that allows unimpeded early viral replication. Viral kinetics do not differ between controls and vaccinees during this delay phase. An increase in virus-specific CD8+ T-cell numbers around day 10 postinfection coincides with a slowing in viral replication in vaccinees and reduces peak viral loads by around 1 log. However, this response is too little too late to prevent establishment of persistent infection.

FIG. 1.

Outcome of acute SHIV-89.6P infection. Viral load (top panels) and number of p11c⁺ T cells (bottom panels) are shown for individual monkeys (black lines). (a and b) Mean viral growth rates for control (a) and vaccinated (b) monkeys prior to day 10 (blue lines) and after day 10 (red lines) are shown. Viral clearance rates are shown in green. (c and d) Average p11c⁺ T-cell expansion rates (blue lines) and double exponential decay results (red lines) for control (c) and vaccinated (d) monkeys are shown.

FIG. 2.

Higher T-cell affinity and early viral control (schematic). The early trajectories of viral loads are similar between control (solid lines) and vaccinated (dashed lines) animals. CD8⁺ T cells are activated once a threshold level of infection (dotted lines) is reached (top panel). Once activated, T cells exert their effects and control viral growth. Increased affinity of the responding CD8⁺ T cells leads to a reduced threshold for stimulation, earlier T-cell activation, and faster viral control (bottom panel).