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Skewed maturation of memory HIV-specific CD8 T lymphocytes

Item Type:Article
Title:Skewed maturation of memory HIV-specific CD8 T lymphocytes
Creators Name:Champagne, P. and Ogg, G.S. and King, A.S. and Knabenhans, C. and Ellefsen, K. and Nobile, M. and Appay, V. and Rizzardi, G.P. and Fleury, S. and Lipp, M. and Foerster, R. and Rowland-Jones, S. and Sekaly, R.P. and McMichael, A.J. and Pantaleo, G.
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 capacities 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+ --> CD45RA- 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.
Keywords:CD45 Antigens, CD8-Positive T-Lymphocytes, Cell Division, Cell Lineage, Cytomegalovirus, T-Lymphocyte Epitopes, HIV, HIV Infections, Immunologic Memory, Immunophenotyping, Interferon-gamma, Leukopoiesis, Membrane Glycoproteins, Perforin, Pore Forming Cytotoxic Proteins, CCR7 Receptors, Chemokine Receptors, T-Lymphocyte Subsets
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:410
Number:6824
Page Range:106-111
Date:1 March 2001
Official Publication:https://doi.org/10.1038/35065118
PubMed:View item in PubMed

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