TY - JOUR
T1 - CXCL12 prolongs naive CD4 + T lymphocytes survival via activation of PKA, CREB and Bcl2 and BclXl up-regulation
AU - Vitiello, Laura
AU - Ferraro, Elisabetta
AU - De Simone, Salvatore
AU - Gatta, Lucia
AU - Feraco, Alessandra
AU - Racioppi, Luigi
AU - Rosano, Giuseppe
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - Complex patient rehabilitation
KW - CXCL12
KW - Immune system
KW - Lymphocytes survival
KW - Naive T lymphocytes
KW - SDF-1α
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U2 - 10.1016/j.ijcard.2016.09.007
DO - 10.1016/j.ijcard.2016.09.007
M3 - Article
AN - SCOPUS:84992051965
VL - 224
SP - 206
EP - 212
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
ER -