title: Progression to CMV end-organ disease in HIV-1-infected individuals despite abundance of highly differentiated CMV-specific CD8+ T-cells.
abstract: Since CMV-specific T-cells have been shown to generally express an advanced state of differentiation, we investigated whether these mature CMV-specific T-cells are sustained in HIV-infected patients, who are not treated with HAART, receive no CMV medication, but do progress to AIDS with CMV end-organ disease (AIDS-CMV). CD8+ and CD4+ T-cell phenotype was studied in these patients in comparison with long-term asymptomatic HIV-infected individuals, progressors to AIDS without CMV end-organ disease as well as CMV-seropositive HIV-negative controls. CMV-specific CD8+ T-cells from progressors to AIDS-CMV expressed markers typical of highly differentiated effector T-cells, being CCR7-, CD27- CD45RO+/-, with high CD57 expression and increased Ki67 expression, compatible with functional effector cell capabilities. In addition, CD4+ T-cells with the characteristic CD27-CD28- phenotype previously shown to be induced by CMV infection specifically, were found in very high numbers in the HIV+ individuals, but the highest in progressors to AIDS-CMV just before onset of disease. Also the normally rare CD45RO-CD27-CD4+ subset increased significantly, whereas the CD45RO-CD27+CD4+ subset decreased. Our data show that in patients progressing to AIDS-CMV, CMV-specific CD8+ T-cells have expanded and are fully differentiated to mature functional effector T-cells. These cells are not protective apparently, but may contribute to tissue-associated immunopathology characteristic of these clinical conditions.
authors.affiliation: Department of Clinical Viro-Immunology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Bronke
authors.forename: G H A
authors.initials: GH
authors.lastname: Westerlaken
authors.forename: F
authors.initials: F
authors.lastname: Miedema
authors.forename: K
authors.initials: K
authors.lastname: Tesselaar
authors.forename: D
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000821:virology*; D018450:Disease Progression; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D013997:Time Factors
chemical_list: D015703:Antigens, CD; C515370:CCR7 protein, human; D019394:Ki-67 Antigen; D054400:Receptors, CCR7; D019707:Receptors, Chemokine