Why Don't CD8+ T Cells Reduce the Lifespan of SIV-Infected Cells In Vivo?

Abstract

In January 2010 two groups independently published the observation that the depletion of CD8+ cells in SIV-infected macaques had no detectable impact on the lifespan of productively infected cells. This unexpected observation led the authors to suggest that CD8+ T cells control SIV viraemia via non-lytic mechanisms. However, a number of alternative plausible explanations, compatible with a lytic model of CD8+ T cell control, were proposed. This left the field with no consensus on how to interpret these experiments and no clear indication whether CD8+ T cells operated primarily via a lytic or a non-lytic mechanism. The aim of this work was to investigate why CD8+ T cells do not appear to reduce the lifespan of SIV-infected cells in vivo.

Author Summary

Several studies have shown a role for CD8+ T cells in controlling SIV-infection. However, early last year two groups independently showed that depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of productively infected cells, suggesting that direct cell killing may not be the major mechanism of antiviral activity by CD8+ lymphocytes. We investigated whether the lack of an effect on lifespan of infected cells indeed excludes a lytic role for CD8+ cells and whether a non-lytic effect of CD8+ cells, for instance by preventing new infections or blocking production of free virions, better explains the similar death rates of SIV-infected cells in animals with and without CD8+ lymphocytes. We found that, even though lytic models of CD8+ cell function are compatible with the absence of an effect of CD8+ cells on the lifespan of productively infected cells, the most likely mechanism of CD8-control in SIV-infection is via a non-lytic mechanism.