title: Dynamics of T cell responses in HIV infection.
abstract: 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.
authors.affiliation: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom. vappay@gwmail.jr2.ox.ac.uk
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
authors.forename: Laura
authors.initials: L
authors.lastname: Papagno
authors.forename: Celsa A
authors.initials: CA
authors.lastname: Spina
authors.forename: Pokrath
authors.initials: P
authors.lastname: Hansasuta
authors.forename: Abigail
authors.initials: A
authors.lastname: King
authors.forename: Louise
authors.initials: L
authors.lastname: Jones
authors.forename: Graham S
authors.initials: GS
authors.lastname: Ogg
authors.forename: Susan
authors.initials: S
authors.lastname: Little
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
mesh_terms: D000208:Acute Disease; D000956:Antigens, Viral / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002908:Chronic Disease; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology* / Q000821:virology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte