title: Lymphocytic alveolitis is associated with the accumulation of functionally impaired HIV-specific T cells in the lung of antiretroviral therapy-naive subjects.
abstract: BACKGROUND
  Lymphocytic alveolitis in HIV-1-infected individuals is associated with multiple pulmonary complications and a poor prognosis. Although lymphocytic alveolitis has been associated with viremia and an increased number of CD8(+) T cells in the lung, its exact cause is unknown.
  
  
  OBJECTIVE
  To determine if HIV-1-specific T cells are associated with lymphocytic alveolitis in HIV-1-infected individuals.
  
  
  METHODS
  Using blood and bronchoalveolar lavage (BAL) cells from normal control subjects and untreated HIV-1-infected individuals, we examined the frequency and functional capacity of HIV-1-specific T cells.
  
  
  RESULTS
  We found that HIV-1-specific T cells were significantly elevated in the BAL compared with blood of HIV-1-infected individuals and strongly correlated with T-cell alveolitis. Expression of Ki67, a marker of in vivo proliferation, was significantly reduced on HIV-1-specific T cells in BAL compared with blood, suggesting a diminished proliferative capacity. In addition, HIV-1-specific CD4(+) and CD8(+) T cells in BAL had higher expression of programmed death 1 (PD-1) and lower cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression than those in the blood. A strong correlation between PD-1, but not CTLA-4, and HIV-1-specific T-cell proliferation was seen, and blockade of the PD-1/PD-L1 pathway augmented HIV-1-specific T-cell proliferation, suggesting that the PD-1 pathway was the main cause of reduced proliferation in the lung.
  
  
  CONCLUSIONS
  These findings suggest that alveolitis associated with HIV-1 infection is caused by the recruitment of HIV-1-specific CD4(+) and CD8(+) T cells to the lung. These antigen-specific T cells display an impaired proliferative capacity that is caused by increased expression of PD-1.
authors.affiliation: 1 Department of Medicine.
authors.forename: C Preston
authors.initials: CP
authors.lastname: Neff
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Chain
authors.forename: Samantha
authors.initials: S
authors.lastname: MaWhinney
authors.forename: Allison K
authors.initials: AK
authors.lastname: Martin
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Linderman
authors.forename: Sonia C
authors.initials: SC
authors.lastname: Flores
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Campbell
authors.forename: Brent E
authors.initials: BE
authors.lastname: Palmer
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Fontenot
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D016022:Case-Control Studies; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology / Q000821:virology; D008171:Lung Diseases / Q000276:immunology / Q000821:virology*; D008213:Lymphocyte Activation / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015488:HIV Antigens; D061026:Programmed Cell Death 1 Receptor
keywords: HIV; T cells; cytokines; lung; programmed cell death 1 receptor