• C Preston Neff, Jennifer L Chain, Samantha MaWhinney, Allison K Martin, Derek J Linderman, Sonia C Flores, Thomas B Campbell, Brent E Palmer, and Andrew P Fontenot.
• 1 Department of Medicine.
• Am. J. Respir. Crit. Care Med. 2015 Feb 15; 191 (4): 464-73.

RationaleLymphocytic 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.ObjectivesTo determine if HIV-1-specific T cells are associated with lymphocytic alveolitis in HIV-1-infected individuals.MethodsUsing 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 ResultsWe 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.ConclusionsThese 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.

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