Smoking and human immunodeficiency virus 1 infection promote retention of CD8+ T cells in the airway mucosa

GND
1223547914
Affiliation
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Harvard University, Charlestown, United States
Corleis, Björn;
Affiliation
Division of Pulmonary Critical Care and Occupational Medicine, Department of Internal Medicine, College ofMedicine, University of Iowa, Iowa City, United States
Cho, Josalyn L.;
Affiliation
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, United States
Gates, Samantha J.;
Affiliation
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, United States
Linder, Alice H.;
Affiliation
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, United States
Dickey, Amy;
Affiliation
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, United States
Lisanti-Park, Antonella C.;
Affiliation
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, United States
Schiff, Abigail E.;
Affiliation
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, United States
Ghebremichael, Musie;
Affiliation
Division of Pulmonary and Critical Care Medicine, Department of InternalMedicine, Massachusetts General Hospital, Boston, United States
Kohli, Puja;
Affiliation
Division of Pulmonary and Critical Care Medicine, Department of InternalMedicine, Massachusetts General Hospital, Boston, United States
Winkler, Tilo;
Affiliation
Division of Pulmonary and Critical Care Medicine, Department of InternalMedicine, Massachusetts General Hospital, Boston, United States
Harris, R. Scott;
Affiliation
Division of Pulmonary and Critical Care Medicine, Department of InternalMedicine, Massachusetts General Hospital, Boston, United States
Medoff, Benjamin D.;
Affiliation
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, United States
Kwon, Douglas S.

Smoking and human immunodeficiency virus 1 (HIV-1) infection are risk factors for chronic obstructive pulmonary disease (COPD), which is among the most common comorbid conditions in people living with HIV-1. HIV-1 infection leads to persistent expansion of CD8+ T cells, and CD8+ T cell-mediated inflammation has been implicated in COPD pathogenesis. In this study, we investigated the effects of HIV-1 infection and smoking on T-cell dynamics in patients at risk of COPD. BAL fluid, endobronchial brushings, and blood from HIV-1 infected and uninfected nonsmokers and smokers were analyzed by flow cytometry, and lungs were imaged by computed tomography. Chemokines were measured in BAL fluid, and CD8+ T-cell chemotaxis in the presence of cigarette smoke extract was assessed in vitro. HIV-1 infection increased CD8+ T cells in the BAL fluid, but this increase was abrogated by smoking. Smokers had reduced BAL fluid concentrations of the T cell-recruiting chemokines CXCL10 and CCL5, and cigarette smoke extract inhibited CXCL10 and CCL5 production by macrophages and CD8+ T-cell transmigration in vitro. In contrast to the T cells in BAL fluid, CD8+ T cells in endobronchial brushings were increased in HIV-1-infected smokers, which was driven by an accumulation of effector memory T cells in the airway mucosa and an increase in tissue-resident memory T cells. Mucosal CD8+ T-cell numbers inversely correlated with lung aeration, suggesting an association with inflammation and remodeling. HIV-1 infection and smoking lead to retention of CD8+ T cells within the airway mucosa.

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