title: Characterization of CD4(+) CTLs ex vivo.
abstract: The cytotoxic potential of CD8(+) T cells and NK cells plays a crucial role in the immune response to pathogens. Although in vitro studies have reported that CD4(+) T cells are also able to mediate perforin-mediated killing, the in vivo existence and relevance of cytotoxic CD4(+) T cells have been the subject of debate. Here we show that a population of CD4(+) perforin(+) T cells is present in the circulation at low numbers in healthy donors and is markedly expanded in donors with chronic viral infections, in particular HIV infection, at all stages of the disease, including early primary infection. Ex vivo analysis shows that these cells have cytotoxic potential mediated through the release of perforin. In comparison with more classical CD4(+) T cells, this subset displays a distinct surface phenotype and functional profile most consistent with end-stage differentiated T cells and include Ag experienced CD4(+) T cells. The existence of CD4(+) cytotoxic T cells in vivo at relatively high levels in chronic viral infection suggests a role in the immune response.
authors.affiliation: Medical Research Council Human Immunology Unit, 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: John J
authors.initials: JJ
authors.lastname: Zaunders
authors.forename: Laura
authors.initials: L
authors.lastname: Papagno
authors.forename: Julian
authors.initials: J
authors.lastname: Sutton
authors.forename: Angel
authors.initials: A
authors.lastname: Jaramillo
authors.forename: Anele
authors.initials: A
authors.lastname: Waters
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: Pat
authors.initials: P
authors.lastname: Grey
authors.forename: Don
authors.initials: D
authors.lastname: Smith
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
mesh_terms: D015704:CD4 Antigens / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin