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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.

Original publication




Journal article


J Immunol

Publication Date





3660 - 3666


Acute Disease, Antigens, Viral, Apoptosis, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Differentiation, Chronic Disease, Disease Progression, Epitopes, T-Lymphocyte, HIV Infections, HIV-1, Humans, Immunologic Memory, Immunophenotyping, Lymphocyte Activation, Lymphocyte Count, T-Lymphocyte Subsets