Dynamics of T cell responses in HIV infection.
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.
Appay
Victor
V
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom. vappay@gwmail.jr2.ox.ac.uk
Papagno
Laura
L
Spina
Celsa A
CA
Hansasuta
Pokrath
P
King
Abigail
A
Jones
Louise
L
Ogg
Graham S
GS
Little
Susan
S
McMichael
Andrew J
AJ
Richman
Douglas D
DD
Rowland-Jones
Sarah L
SL
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
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte