title: Selective decrease in circulating V alpha 24+V beta 11+ NKT cells during HIV type 1 infection.
abstract: CD1d-restricted NKT cells express an invariant TCR and have been demonstrated to play an important regulatory role in a variety of immune responses. Invariant NKT cells down-regulate autoimmune responses by production of type 2 cytokines and can initiate antitumor and antimicrobial immune responses by production of type 1 cytokines. Although defects in the (invariant) Valpha24+Vbeta11+ NKT cell population have been observed in patients with cancer and autoimmune diseases, little is known regarding the protective role of Valpha24+Vbeta11+ NKT cells in human infectious disease. In a cross-sectional study in HIV-1-infected individuals, we found circulating numbers of Valpha24+Vbeta11+ NKT cells to be reduced, independent of CD4+ T cell counts, CD4:CD8 ratios, and viral load. Because a small minority of Valpha24+Vbeta11+ NKT cells of healthy donors expressed HIV-1 (co)receptors and the vast majority of Valpha24+Vbeta11+ NKT cells in HIV-1-infected individuals expressed the Fas receptor, the depletion was more likely due to Fas-mediated apoptosis than to preferential infection of Valpha24+Vbeta11+ NKT cells by HIV-1. A longitudinal cohort study, in which patients were analyzed before seroconversion and 1 and 5 years after seroconversion, demonstrated that a large proportion of the depletion occurred within the first year postseroconversion. In this longitudinal study no evidence was found to support an important role of Valpha24+Vbeta11+ NKT cells in determining the rate of progression during HIV-1 infection.
authors.affiliation: Department of Medical Oncology, Pathology, and Internal Medicine, Free University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Hans J J
authors.initials: HJ
authors.lastname: van der Vliet
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: Mette D
authors.initials: MD
authors.lastname: Hazenberg
authors.forename: Nobusuke
authors.initials: N
authors.lastname: Nishi
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Otto
authors.forename: Birgit H
authors.initials: BH
authors.lastname: van Benthem
authors.forename: Maria
authors.initials: M
authors.lastname: Prins
authors.forename: Frans A
authors.initials: FA
authors.lastname: Claessen
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Herbert M
authors.initials: HM
authors.lastname: Pinedo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015704:CD4 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000097:blood; D019713:Receptors, CCR5 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D015704:CD4 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019713:Receptors, CCR5; D019014:fas Receptor