title: Distribution and functional analysis of memory antiviral CD8 T cell responses in HIV-1 and cytomegalovirus infections.
abstract: In the present study, we have investigated the anatomic distribution and the function of different populations of HIV-1- and cytomegalovirus (CMV)-specific memory CD8 T cells. The different populations of virus-specific memory CD8 T cells were distinguished on the basis of the expression of CD45RA and CCR7, and the composition of HIV-1- and CMV-specific memory CD8 T cell pools were compared in subjects with chronic HIV-1 and CMV co-infection. The distribution of HIV-1-specific CD8 T cells was similar between blood and lymph node. However, CMV-specific CD8 T cells were accumulated predominantly in the blood away from the lymphoid tissue. The majority (>70%) of HIV-1- and CMV-specific CD8 T cells in both blood and lymph node had a phenotype, e.g. CCR7-, typical of effector T cells. HIV-1-specific memory CD8 T cells were mostly (>80%) pre-terminally differentiated cells, e.g. CD45RA-CCR7-, in both blood and lymph node while 30-50% of CMV-specific CD8 T cells were terminally differentiated, e.g. CD45RA+CCR7-. Therefore, consistently with studies in mice, antigen-specific effector memory CD8 T cells accumulate predominantly in the target organ of the pathogen in humans, and the differences in the composition of HIV-1- and CMV-specific CD8 T cell pools were also present in the lymphoid tissue. A substantial proportion (30-40%) of virus-specific CD8+CCR7+ T cells produced IFN-gamma. Thus, indicating that the expression of CCR7 does not provide a clear-cut separation of memory CD8 T cells with distinct functional capacities. Taken together, these results provide further advances in the characterization of human memory CD8 T cells.
authors.affiliation: Laboratory of AIDS Immunopathogenesis, Divisions of Immunology and Allergy and Infectious Diseases, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
authors.forename: Kim
authors.initials: K
authors.lastname: Ellefsen
authors.forename: Alexandre
authors.initials: A
authors.lastname: Harari
authors.forename: Patrick
authors.initials: P
authors.lastname: Champagne
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Bart
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sékaly
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens