title: CXCL12 prolongs naive CD4+ T lymphocytes survival via activation of PKA, CREB and Bcl2 and BclXl up-regulation.
abstract: BACKGROUND
  Naive T lymphocytes recirculate through the body, traveling from secondary lymphoid organs through tissues and via lymphatic vessels and peripheral blood into other secondary lymphoid organs and into the bone marrow. In these tissues, lymphocytes are exposed to the chemokine CXCL12 which is abundantly produced in bone marrow and in lymph nodes by stromal cells. CXCL12 is known to drive lymphocytes chemotaxis and, in cells types such as stem cells, an antiapopototic effect has been described.
  
  
  METHODS
  Here we analyzed the effect of CXCL12 exposure on naïve CD4+ T lymphocytes purified from peripheral blood by immunomagnetic negative isolation and cultured in a nutrient poor medium. We also studied, mainly by western blot analysis, the signaling pathways involved in CXCL12 action on naïve CD4+ T lymphocytes.
  
  
  RESULTS
  We found that CXCL12-exposed cells survived longer than untreated ones and this prolonged lifespan was specific for resting naïve lymphocytes, while in vitro activated lymphoblasts died rapidly despite CXCL12 treatment. We demonstrated that the increased percentage of living cells observed upon CXCL12 administration was not due to induction of proliferation but to a prosurvival effect of this chemokine. Moreover, our data suggest that this prosurvival effect on naïve CD4+ T lymphocytes might likely be mediated by PKA-dependent CREB activation and consequent increased expression of the antiapoptotic factors Bcl2 and BclXl.
  
  
  CONCLUSIONS
  This newly reported activity of CXCL12 might contribute to the maintenance of the naïve T lymphocytes pool in vivo, which is needed to ensure a proper immune response to new antigens.
authors.affiliation: Laboratory of Pathophysiology of Cachexia and Metabolism of Skeletal Muscle, IRCCS San Raffaele Pisana, 00166, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Vitiello
authors.affiliation: Laboratory of Pathophysiology of Cachexia and Metabolism of Skeletal Muscle, IRCCS San Raffaele Pisana, 00166, Rome, Italy. Electronic address: elisabetta.ferraro@sanraffaele.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferraro
authors.affiliation: Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Napoli, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Simone
authors.affiliation: Laboratory of Pathophysiology of Cachexia and Metabolism of Skeletal Muscle, IRCCS San Raffaele Pisana, 00166, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gatta
authors.affiliation: Laboratory of Pathophysiology of Cachexia and Metabolism of Skeletal Muscle, IRCCS San Raffaele Pisana, 00166, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Feraco
authors.affiliation: Department of Medicine, Duke University, Durham, NC, USA; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Racioppi
authors.affiliation: Laboratory of Pathophysiology of Cachexia and Metabolism of Skeletal Muscle, IRCCS San Raffaele Pisana, 00166, Rome, Italy; Cardiovascular and Cell Sciences Institute, St George's University of London, Cranmer Terrace, London, UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rosano
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D050882:CREB-Binding Protein / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D051020:bcl-X Protein; D050882:CREB-Binding Protein; D011494:Protein Kinases
keywords: CXCL12; Complex patient rehabilitation; Immune system; Lymphocytes survival; Naive T lymphocytes; SDF-1α