title: Preferential depletion of gut CD4-expressing iNKT cells contributes to systemic immune activation in HIV-1 infection.
abstract: Chronic inappropriate immune activation is the central defect-driving loss of CD4(+) T helper cells and progression to AIDS in persons with HIV-1 infection, but the mechanisms remain controversial. We examined key regulatory invariant receptor natural killer T (iNKT) cells in the gut, the largest reservoir of lymphocytes and a key arena of HIV-1 pathogenesis. In healthy control persons, the anti-inflammatory CD4(+) iNKT-cell subset predominated over the pro-inflammatory CD4(-) iNKT-cell subset in the gut, but not in the blood, compartment. HIV-1 infection resulted in a preferential loss of this anti-inflammatory CD4(+) iNKT-cell subset within the gut. The degree of loss of the CD4(+) iNKT-cell subset in the gut, but not in the blood, correlated to the systemic immune activation and exhaustion that have been linked to disease progression. These results suggest a potentially important contribution of gut iNKT-cell imbalance in determining the systemic immune activation that is the hallmark of HIV-1 pathogenesis.
authors.affiliation: Department of Medicine and UCLA AIDS Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Ibarrondo
authors.forename: S B
authors.initials: SB
authors.lastname: Wilson
authors.forename: L E
authors.initials: LE
authors.lastname: Hultin
authors.forename: R
authors.initials: R
authors.lastname: Shih
authors.forename: M A
authors.initials: MA
authors.lastname: Hausner
authors.forename: P M
authors.initials: PM
authors.lastname: Hultin
authors.forename: P A
authors.initials: PA
authors.lastname: Anton
authors.forename: B D
authors.initials: BD
authors.lastname: Jamieson
authors.forename: O O
authors.initials: OO
authors.lastname: Yang
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D016923:Cell Death; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation; D007422:Intestines / Q000276:immunology* / Q000821:virology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000821:virology; D014775:Virus Activation / Q000276:immunology; D055815:Young Adult
chemical_list: D015704:CD4 Antigens