title: Severe functional impairment and elevated PD-1 expression in CD1d-restricted NKT cells retained during chronic HIV-1 infection.
abstract: Invariant CD1d-restricted NKT cells play important roles in regulating both innate and adaptive immunity. They are targeted by HIV-1 infection and severely reduced in number or even lost in many infected subjects. Here, we have investigated the characteristics of NKT cells retained by some patients despite chronic HIV-1 infection. NKT cells preserved under these circumstances displayed an impaired ability to proliferate and produce IFN-gamma in response to CD1d-restricted lipid antigen as compared with cells from uninfected control subjects. HIV-1 infection was associated with an elevated expression of the inhibitory programmed death-1 (PD-1) receptor (CD279) on the CD4(-) subset of NKT cells. However, blocking experiments indicated that the functional defects in NKT cells were largely PD-1-independent. Furthermore, the elevated PD-1 expression and the functional defects were not restored by anti-retroviral treatment, and the NKT cell numbers in blood did not recover significantly in response to treatment. The functional phenotype of NKT cells in these patients suggests an irreversible immune exhaustion due to chronic activation in vivo. The data demonstrate a severe functional impairment in the remaining NKT-cell compartment in HIV-1-infected patients, which limits the prospects to mobilize these cells in immunotherapy approaches in patients.
authors.affiliation: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Moll
authors.forename: Carlotta
authors.initials: C
authors.lastname: Kuylenstierna
authors.forename: Veronica D
authors.initials: VD
authors.lastname: Gonzalez
authors.forename: Sofia K
authors.initials: SK
authors.lastname: Andersson
authors.forename: Lidija
authors.initials: L
authors.lastname: Bosnjak
authors.forename: Anders
authors.initials: A
authors.lastname: Sönnerborg
authors.forename: Máire F
authors.initials: MF
authors.lastname: Quigley
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D055610:Antigens, CD1d / Q000276:immunology* / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002908:Chronic Disease; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor
chemical_list: D015703:Antigens, CD; D055610:Antigens, CD1d; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma