title: Diesel exhaust particle exposure in vitro impacts T lymphocyte phenotype and function.
abstract: BACKGROUND
  Diesel exhaust particles (DEP) are major constituents of ambient air pollution and their adverse health effect is an area of intensive investigations. With respect to the immune system, DEP have attracted significant research attention as a factor that could influence allergic diseases interfering with cytokine production and chemokine expression. With this exception, scant data are available on the impact of DEP on lymphocyte homeostasis. Here, the effects of nanoparticles from Euro 4 (E4) and Euro 5 (E5) light duty diesel engines on the phenotype and function of T lymphocytes from healthy donors were evaluated.
  
  
  METHODS
  T lymphocytes were isolated from peripheral blood obtained from healthy volunteers and subsequently stimulated with different concentration (from 0.15 to 60 μg/ml) and at different time points (from 24 h to 9 days) of either E4 or E5 particles. Immunological parameters, including apoptosis, autophagy, proliferation levels, mitochondrial function, expression of activation markers and cytokine production were evaluated by cellular and molecular analyses.
  
  
  RESULTS
  DEP exposure caused a pronounced autophagic-lysosomal blockade, thus interfering with a key mechanism involved in the maintaining of T cell homeostasis. Moreover, DEP decreased mitochondrial membrane potential but, unexpectedly, this effect did not result in changes of the apoptosis and/or necrosis levels, as well as of intracellular content of adenosine triphosphate (ATP). Finally, a down-regulation of the expression of the alpha chain of the interleukin (IL)-2 receptor (i.e., the CD25 molecule) as well as an abnormal Th1 cytokine expression profile (i.e., a decrease of IL-2 and interferon (IFN)-γ production) were observed after DEP exposure. No differences between the two compounds were detected in all studied parameters.
  
  
  CONCLUSIONS
  Overall, our data identify functional and phenotypic T lymphocyte parameters as relevant targets for DEP cytotoxicity, whose impairment could be detrimental, at least in the long run, for human health, favouring the development or the progression of diseases such as autoimmunity and cancer.
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. marina.pierdominici@iss.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Pierdominici
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. angela.maselli@iss.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Maselli
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. serena.cecchetti@iss.it.
authors.forename: Serena
authors.initials: S
authors.lastname: Cecchetti
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy. antonella.tinari@iss.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Tinari
authors.affiliation: San Gallicano Dermatologic Institute, IRCCS-IFO, Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, Rome, Italy. mastrofrancesco@ifo.it.
authors.forename: Arianna
authors.initials: A
authors.lastname: Mastrofrancesco
authors.affiliation: Istituto di Ricerche sulla Combustione (IRC), CNR- Naples, Italy. alfe@irc.cnr.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Alfè
authors.affiliation: Istituto di Ricerche sulla Combustione (IRC), CNR- Naples, Italy. vale.gargiulo@gmail.com.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gargiulo
authors.affiliation: Istituto Motori (IM), CNR-Naples, Italy. c.beatrice@im.cnr.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Beatrice
authors.affiliation: Istituto Motori (IM), CNR-Naples, Italy. g.diblasio@im.cnr.it.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Di Blasio
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. giulia.carpinelli@iss.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Carpinelli
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. elena.ortona@iss.it.|Istituto San Raffaele Sulmona, Sulmona, Italy. elena.ortona@iss.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Ortona
authors.affiliation: Department of Clinical Medicine, Division of Clinical Immunology, Sapienza University of Rome, Rome, Italy. antonello.giovannetti@uniroma1.it.
authors.forename: Antonello
authors.initials: A
authors.lastname: Giovannetti
authors.affiliation: Department of Clinical Medicine, Division of Clinical Immunology, Sapienza University of Rome, Rome, Italy. silvana.fiorito@uniroma1.it.|Institute of Translational Pharmacology, CNR-Rome, Italy. silvana.fiorito@uniroma1.it.|Research Center for Nanotechnologies applied to Engineering-CNIS, Rome, Italy. silvana.fiorito@uniroma1.it.
authors.forename: Silvana
authors.initials: S
authors.lastname: Fiorito
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D001343:Autophagy / Q000187:drug effects; D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008875:Middle Aged; D010316:Particle Size; D053260:Soot / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053260:Soot; D001335:Vehicle Emissions