Lymphocytic alveolitis is associated with the accumulation of functionally impaired HIV-specific T cells in the lung of antiretroviral therapy-naive subjects

Am J Respir Crit Care Med. 2015 Feb 15;191(4):464-73. doi: 10.1164/rccm.201408-1521OC.


Rationale: 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.

Objectives: 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.

Measurements and main 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.

Keywords: HIV; T cells; cytokines; lung; programmed cell death 1 receptor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers / metabolism
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoalveolar Lavage Fluid / virology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / virology
  • Case-Control Studies
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • HIV Antigens / immunology
  • HIV Infections / complications
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Lung / immunology
  • Lung / virology
  • Lung Diseases / immunology
  • Lung Diseases / virology*
  • Lymphocyte Activation / immunology
  • Programmed Cell Death 1 Receptor / metabolism


  • Biomarkers
  • HIV Antigens
  • Programmed Cell Death 1 Receptor