Skewed maturation of memory HIV-specific CD8 T lymphocytes

Patrick Champagne, Graham S. Ogg, Abigail S. King, Christian Knabenhans, Kim Ellefsen, Massimo Nobile, Victor Appay, G. Paolo Rizzardi, Sylvain Fleury, Martin Lipp, Reinhold Förster, Sarah Rowland-Jones, Rafick-P. Sékaly, Andrew J. McMichael and Giuseppe Pantaleo ()
Additional contact information
Patrick Champagne: Laboratory of AIDS Immunopathogenesis, Centre Hospitalier Universitaire Vaudois, University of Lausanne
Graham S. Ogg: MRC Human Immunology Unit, Institute for Molecular Medicine, John Radcliffe Hospital
Abigail S. King: MRC Human Immunology Unit, Institute for Molecular Medicine, John Radcliffe Hospital
Christian Knabenhans: Laboratory of AIDS Immunopathogenesis, Centre Hospitalier Universitaire Vaudois, University of Lausanne
Kim Ellefsen: Laboratory of AIDS Immunopathogenesis, Centre Hospitalier Universitaire Vaudois, University of Lausanne
Massimo Nobile: Laboratory of AIDS Immunopathogenesis, Centre Hospitalier Universitaire Vaudois, University of Lausanne
Victor Appay: MRC Human Immunology Unit, Institute for Molecular Medicine, John Radcliffe Hospital
G. Paolo Rizzardi: Laboratory of AIDS Immunopathogenesis, Centre Hospitalier Universitaire Vaudois, University of Lausanne
Sylvain Fleury: Laboratory of AIDS Immunopathogenesis, Centre Hospitalier Universitaire Vaudois, University of Lausanne
Martin Lipp: Molecular Tumor genetics and Immunogenetics, Max-Delrbrück-Center for Molecular Medicine
Reinhold Förster: Molecular Tumor genetics and Immunogenetics, Max-Delrbrück-Center for Molecular Medicine
Sarah Rowland-Jones: MRC Human Immunology Unit, Institute for Molecular Medicine, John Radcliffe Hospital
Rafick-P. Sékaly: Laboratoire d’Immunologie, Centre de Recherche du Centre Hospitalier de l’Université de Montréal
Andrew J. McMichael: MRC Human Immunology Unit, Institute for Molecular Medicine, John Radcliffe Hospital
Giuseppe Pantaleo: Laboratory of AIDS Immunopathogenesis, Centre Hospitalier Universitaire Vaudois, University of Lausanne

Nature, 2001, vol. 410, issue 6824, 106-111

Abstract: Abstract Understanding the lineage differentiation of memory T cells is a central question in immunology. We investigated this issue by analysing the expression of the chemokine receptor CCR7, which defines distinct subsets of naive and memory T lymphocytes with different homing and effector capacities1,2,3 and antiviral immune responses to HIV and cytomegalovirus. Ex vivo analysis of the expression of CD45RA and CCR7 antigens, together with in vitro analysis of the cell-division capacity of different memory CD8+ T-cell populations, identified four subsets of HIV- and CMV-specific CD8+ T lymphocytes, and indicated the following lineage differentiation pattern: CD45RA+CCR7+ → CD45RA-CCR7+ → CD45RACD45RA-CCR7- → CD45RA+CCR7-. Here we demonstrate through analysis of cell division (predominantly restricted to the CCR7+CD8+ T-cell subsets) that the differentiation of antigen-specific CD8+ T cells is a two-step process characterized initially by a phase of proliferation largely restricted to the CCR7+CD8+ cell subsets, followed by a phase of functional maturation encompassing the CCR7-CD8+ cell subsets. The distribution of these populations in HIV- and CMV-specific CD8+ T cells showed that the HIV-specific cell pool was predominantly (70%) composed of pre-terminally differentiated CD45RA-CCR7- cells, whereas the CMV-specific cell pool consisted mainly (50%) of the terminally differentiated CD45RA+CCR7- cells. These results demonstrate a skewed maturation of HIV-specific memory CD8+ T cells during HIV infection.

Date: 2001
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DOI: 10.1038/35065118

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