Dynamics of T cell responses in HIV infection
Appay V., Papagno L., Spina CA., Hansasuta P., King A., Jones L., Ogg GS., Little S., McMichael AJ., Richman DD., Rowland-Jones SL.
Cytotoxic CD8+ T cells play a major role in the immune response against viruses. However, the dynamics of CD8+ T cell responses during the course of a human infection are not well understood. Using tetrameric complexes in combination with a range of intracellular and extracellular markers, we present a detailed analysis of the changes in activation and differentiation undergone by Ag-specific CD8+ T cells, in relation to Ag-specific CD4+ T cell responses, in the context of a human infection: HIV-1. During primary HIV-1 infection, the initial population of HIV-specific CD8+ T cells is highly activated and prone to apoptosis. The Ag-specific cells differentiate rapidly from naive to cells at a perforin low intermediate stage of differentiation, later forming a stable pool of resting cells as viral load decreases during chronic infection. These observations have significant implications for our understanding of T cell responses in human viral infections in general and indicate that the definition of effector and memory subsets in humans may need revision.