title: High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage.
abstract: The mechanisms underlying the massive gastrointestinal tract CD4 T-cell depletion in human immunodeficiency virus (HIV) infection are not well understood nor is it clear whether similar depletion is manifest at other mucosal surfaces. Studies of T-cell and virus dynamics in different anatomical sites have begun to illuminate the pathogenesis of HIV-associated disease. Here, we studied depletion and HIV infection frequencies of CD4 T cells from the gastrointestinal tract, bronchoalveolar lavage (BAL), and blood with the frequencies and functional profiles of HIV-specific T cells in these anatomically distinct sites in HIV-infected individuals. The major findings to emerge were as follows: (i) depletion of gastrointestinal CD4 T cells is associated with high frequencies of infected CD4 T cells; (ii) HIV-specific T cells are present at low frequencies in the gastrointestinal tract compared to blood; (iii) BAL CD4 T cells are not massively depleted during the chronic phase; (iv) infection frequencies of BAL CD4 T cells are similar to those in blood; (v) significantly higher frequencies and increased functionality of HIV-specific T cells were observed in BAL compared to blood. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might circumvent global depletion of mucosal CD4 T cells.
authors.affiliation: Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: K S
authors.initials: KS
authors.lastname: Knox
authors.forename: A I
authors.initials: AI
authors.lastname: Asher
authors.forename: D A
authors.initials: DA
authors.lastname: Price
authors.forename: L M
authors.initials: LM
authors.lastname: Kohli
authors.forename: E
authors.initials: E
authors.lastname: Gostick
authors.forename: B J
authors.initials: BJ
authors.lastname: Hill
authors.forename: C A
authors.initials: CA
authors.lastname: Hage
authors.forename: Z
authors.initials: Z
authors.lastname: Brahmi
authors.forename: A
authors.initials: A
authors.lastname: Khoruts
authors.forename: H L
authors.initials: HL
authors.lastname: Twigg
authors.forename: T W
authors.initials: TW
authors.lastname: Schacker
authors.forename: D C
authors.initials: DC
authors.lastname: Douek
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D006678:HIV / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D009928:Organ Specificity / Q000276:immunology