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The Journal of Immunology, 2002, 168: 3660-3666.
Copyright © 2002 by The American Association of Immunologists

Dynamics of T Cell Responses in HIV Infection1

Victor Appay2,*, Laura Papagno*, Celsa A. Spina{dagger}, Pokrath Hansasuta*, Abigail King*, Louise Jones*, Graham S. Ogg*, Susan Little{dagger}, Andrew J. McMichael*, Douglas D. Richman{dagger} and Sarah L. Rowland-Jones*

* Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom; and {dagger} Veterans Affairs Research Center for AIDS and HIV Infection, University of California at San Diego, La Jolla, CA 92093

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.




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