title: Relationships of pulmonary function, inflammation, and T-cell activation and senescence in an HIV-infected cohort.
abstract: OBJECTIVE
  To determine associations between circulating markers of immune activation, immune cell senescence, and inflammation with HIV-associated abnormalities of pulmonary function.
  
  
  METHODS
  HIV infection is an independent risk factor for abnormal pulmonary function. Immune activation, immune senescence, and chronic inflammation are characteristics of chronic HIV infection that have been associated with other HIV-associated comorbidities and may be related to pulmonary disease in this population.
  
  
  METHODS
  Participants from an HIV-infected cohort (n = 147) completed pulmonary function testing (PFT). Markers of T-cell activation and senescence were determined by flow cytometry, and plasma levels of interleukin-6, interleukin-8, and C-reactive protein (CRP) were measured, as was telomere length of peripheral blood mononuclear cells (PBMC). Regression models adjusting for clinical risk factors were constructed to examine relationships between biomarkers and PFT outcomes.
  
  
  RESULTS
  Activated CD25(+) T cells and activated/senescent CD69(+)/CD57(+)/CD28(null) CD4(+) T cells, interleukin-6, and CRP were associated with PFT abnormalities. Shortening of PBMC telomere length correlated with airflow obstruction and diffusing impairment. Paradoxically, circulating senescent CD57(+)/CD28(null) CD8(+) T cells were associated with better PFT outcomes.
  
  
  CONCLUSIONS
  Circulating T cells expressing markers of activation and inflammatory cytokine levels are independently correlated with PFT abnormalities in HIV-infected persons. Overall telomere shortening was also associated with pulmonary dysfunction. The paradoxical association of senescent CD8(+) T cells and better PFT outcomes could suggest an unrecognized beneficial compensatory function of such cells or a redistribution of these cells from the circulation to local compartments. Further studies are needed to differentiate and characterize functional subsets of local pulmonary and circulating T-cell populations in HIV-associated pulmonary dysfunction.
authors.affiliation: aDepartment of Medicine bDepartment of Immunology, University of Pittsburgh cUniversity of Pittsburgh Graduate School of Public Health dDepartment of Pediatrics, University of Pittsburgh, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Fitzpatrick
authors.forename: Vikas
authors.initials: V
authors.lastname: Singh
authors.forename: Marnie
authors.initials: M
authors.lastname: Bertolet
authors.forename: Lorrie
authors.initials: L
authors.lastname: Lucht
authors.forename: Cathy
authors.initials: C
authors.lastname: Kessinger
authors.forename: Joshua
authors.initials: J
authors.lastname: Michel
authors.forename: Alison
authors.initials: A
authors.lastname: Logar
authors.forename: Renee
authors.initials: R
authors.lastname: Weinman
authors.forename: Deborah
authors.initials: D
authors.lastname: McMahon
authors.forename: Karen A
authors.initials: KA
authors.lastname: Norris
authors.forename: Abbe N
authors.initials: AN
authors.lastname: Vallejo
authors.forename: Alison
authors.initials: A
authors.lastname: Morris
mesh_terms: D000328:Adult; D000375:Aging; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D008171:Lung Diseases / Q000453:epidemiology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines