Lymphocytic Alveolitis, Bronchoalveolar Lavage Viral Load, and Outcome in Human Immunodeficiency Virus Infection

Twigg, Homer L.; Soliman, Diaa M.; Day, Richard B.; Knox, Kenneth S.; Anderson, Robert; Wilkes, David S.; Schnizlein-Bick, Carol T.

doi:10.1164/ajrccm.159.5.9808031

Cited by 96 publications

(88 citation statements)

References 25 publications

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“…A strong inverse correlation was found between the CD4:CD8 T-cell ratio in blood and peripheral viral load (r = 20.57; P = 0.009) ( Figure 1C), whereas no significant correlation was seen between the CD4:CD8 T-cell ratio in BAL and peripheral viral load (r = 20.30; P = 0.20) (Figure 1D). These findings confirm previous studies (5) and demonstrate that HIV-1-induced lymphocytic alveolitis is primarily caused by CD8 1 T cells.…”

Section: Cd8supporting

confidence: 92%

“…The prevalence of lymphocytic alveolitis is increased in individuals with chronic HIV-1 infection and is associated with pulmonary complications (5). Consistent with these reports, lymphocytic alveolitis with an increase in CD8…”

Section: Discussionsupporting

confidence: 76%

“…Preferential recruitment of CD8 1 T cells to the lung is in part responsible for the imbalance in the CD4:CD8 T-cell ratio that has been associated with HIV-1-specific CTLs and disease progression (5,25). Early studies hypothesized that CTL activity was directed against HIV-1-infected alveolar macrophages that coexpress HIV-1 antigens and CD4 (26).…”

Section: Discussionmentioning

confidence: 99%

“…These complications include chronic obstructive pulmonary disease; pulmonary hypertension; and opportunistic lung infections, such as Pneumocystis pneumonia and tuberculosis (2). Lymphocytic alveolitis usually accompanies these complications and is associated with a poor prognosis (3)(4)(5). Although epidemiologic evidence supports the role of HIV-1 infection in the incidence of lung disease, it is unclear whether this stems from a paucity of CD4 1 T cells or from dysfunctional antigen-specific T-cell responses.…”

mentioning

confidence: 99%

“…1 T-cell count is less than 200 cells per microliter (5). After initiation of HAART, HIV-1 viral load and BAL CD8…”

mentioning

confidence: 99%

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Lymphocytic Alveolitis Is Associated with the Accumulation of Functionally Impaired HIV-Specific T Cells in the Lung of Antiretroviral Therapy–Naive Subjects

Neff¹,

Chain²,

MaWhinney³

et al. 2015

Am J Respir Crit Care Med

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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 1 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 1 and CD8 1 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 1 and CD8 1 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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Section: Cd8supporting

confidence: 92%

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…1 T-cell count is less than 200 cells per microliter (5). After initiation of HAART, HIV-1 viral load and BAL CD8…”

mentioning

confidence: 99%

See 3 more Smart Citations

Lymphocytic Alveolitis Is Associated with the Accumulation of Functionally Impaired HIV-Specific T Cells in the Lung of Antiretroviral Therapy–Naive Subjects

Neff¹,

Chain²,

MaWhinney³

et al. 2015

Am J Respir Crit Care Med

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Lung Immune Defences in the Immunosuppressed Patient

Patel

Koziel

2009

Pulmonary Infection in the Immunocompromised Patient

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Different resistance mutations can be detected simultaneously in the blood and the lung of HIV‐1 infected individuals on antiretroviral therapy

White

Israel-Biet

Coker

et al. 2004

Journal of Medical Virology

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In this retrospective study, matched peripheral blood and lung samples from patients on antiretroviral therapy were studied in order to investigate whether differences in mutations associated with resistance to nucleoside analogues could be detected between the lung and blood. Discordant mutation patterns in the reverse transcriptase (RT) between plasma and cell free bronchoalveolar lavage fluid (BAL-fluid) HIV-1 genomic RNA was observed in five out of seven patients on nucleoside reverse transcriptase inhibitor (NRTI) monotherapy and six out of seven on combination therapy. In the cellular compartments, DNA recovered from peripheral blood mononuclear cells (PBMCs) and cells from BAL-cells discordant HIV-1 resistance genotypes were detected in 15 out of 44 matched samples. Differences in resistant genotypes between PBMCs and BAL-cells were most pronounced in patients receiving combination antiretroviral therapy. The pattern and number of mutations in RT associated with resistance differed in the BAL-cells compared to PBMCs in four out of 12 subjects not receiving antiretroviral therapy at the time of bronchoscopy, three from 14 patients on NRTI monotherapy, five out of nine on dual combination therapy and three out of nine on HAART. The differences in the detection of resistance mutations between blood and the lung suggest that the lung is a site of replication for HIV-1.

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Lymphocytic Alveolitis, Bronchoalveolar Lavage Viral Load, and Outcome in Human Immunodeficiency Virus Infection

Cited by 96 publications

References 25 publications

Lymphocytic Alveolitis Is Associated with the Accumulation of Functionally Impaired HIV-Specific T Cells in the Lung of Antiretroviral Therapy–Naive Subjects

Lymphocytic Alveolitis Is Associated with the Accumulation of Functionally Impaired HIV-Specific T Cells in the Lung of Antiretroviral Therapy–Naive Subjects

Lung Immune Defences in the Immunosuppressed Patient

Different resistance mutations can be detected simultaneously in the blood and the lung of HIV‐1 infected individuals on antiretroviral therapy

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