Involvement of cAMP in CD3 T cell receptor complex- and CD2-mediated apoptosis of human thymocytes.
During intrathymic T cell development, elimination of autoreactive T cell clones by programmed cell death (PCD or apoptosis) is an essential mechanism for self tolerance. The precise intracellular second messengers that lead to this process remain to be determined. In the present work, we show that treatment of freshly isolated thymocytes with an antagonist of the cAMP pathway, the Rp-cAMP, significantly decreases spontaneous death by apoptosis of human thymocytes in vitro. Addition of Rp-cAMP also rescues thymocytes from activation-induced apoptosis following the ligation of surface CD3/T cell receptor complex or CD2 antigens. A cAMP analog, the dibutyryl(Dibut)-cAMP increases PCD of human thymocytes in a dose-dependent manner. Growth and rescue from PCD of thymocytes in the presence of interleukin (IL)-2 or IL-4 are also enhanced by Rp-cAMP and inhibited by Dibut-cAMP. Finally, we detect substantial levels of intracellular cAMP in freshly isolated thymocytes. This study reveals the involvement of cAMP as a second messenger during the apoptosis of normal human thymocytes.
Mentz
F
F
Groupe d'Immuno-Hématologie Moléculaire, CNRS URA625, CHU Pitié-Salpêtrière, Paris, France.
Mossalayi
M D
MD
Ouaaz
F
F
Debré
P
P
D017209:Apoptosis; D018801:CD2 Antigens / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*
D018801:CD2 Antigens; D017252:CD3 Complex; D000242:Cyclic AMP