T cell immunity in acute HIV-1 infection

Abstract

Exceedingly high viral loads and rapid loss of CD4(+) T cells in all tissue compartments are a hallmark of acute human immunodeficiency virus type 1 (HIV-1) infection, which is often accompanied by clinical symptoms such as fever, maculopapular rash, and/or lymphadenopathy. The resolution of the clinical symptoms and the subsequent decrease in plasma viremia are associated with the emergence of HIV-1-specific CD4(+) and CD8(+) T cell responses. The remarkable early inhibition of viremia by CD8(+) T cells appears to be precipitated by only a limited number of specific CD8(+) T cell responses, and the plasma viremia is reduced to a "set point" level. Over time, the breadth and magnitude of CD8(+) T cell responses increase, but without a change in the control of viral replication or further reduction in the viral set point. Moreover, the early viral set point, consequent on the first CD8(+) T cell responses, is highly predictive of the later course of disease progression. Thus, HIV-1-specific CD8(+) T cell responses in acute HIV-1 infection appear uniquely able to efficiently suppress viral replication, whereas CD8(+) T cell responses generated in the chronic phase of infection appear often impaired.

Figure 1. Association of immunodominant CD8+ T cell responses in acute HIV-1 infection and viral set point

Subjects targeting in acute HIV-1 infection a frequent and immunodominant recognized CD8+ T cell epitope have in average a lower early viral set point [7]. In contrast, subjects that do not target immunodominant CD8+ T cell epitopes in acute HIV-1 infection have in average a higher viral set point. This early viral set point is highly predictive for disease outcome.

Figure 2. A schematic model for progressive CD8+ T cell exhaustion and memory development