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

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

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1
1 Department of Medicine.

Abstract

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

Comment in

PMID:
25536276
PMCID:
PMC4351596
DOI:
10.1164/rccm.201408-1521OC
[Indexed for MEDLINE]
Free PMC Article

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