CXCL12 prolongs naive CD4 + T lymphocytes survival via activation of PKA, CREB and Bcl2 and BclXl up-regulation

Laura Vitiello, Elisabetta Ferraro, Salvatore De Simone, Lucia Gatta, Alessandra Feraco, Luigi Racioppi, Giuseppe Rosano

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)206-212
Number of pages7
JournalInternational Journal of Cardiology
Volume224
DOIs
Publication statusPublished - Dec 1 2016

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Keywords

  • Complex patient rehabilitation
  • CXCL12
  • Immune system
  • Lymphocytes survival
  • Naive T lymphocytes
  • SDF-1α

ASJC Scopus subject areas

  • Medicine(all)
  • Cardiology and Cardiovascular Medicine

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