TY - JOUR
T1 - Antagonistic roles for CTLA-4 and the mammalian target of rapamycin in the regulation of clonal anergy
T2 - Enhanced cell cycle progression promotes recall antigen responsiveness
AU - Vanasek, T. L.
AU - Khoruts, Alexander
AU - Zell, T.
AU - Mueller, Daniel L
PY - 2001/11/15
Y1 - 2001/11/15
N2 - CD4+ T cells that undergo multiple rounds of cell division during primary Ag challenge in vivo produce IL-2 on secondary Ag rechallenge, whereas cells that fail to progress through the cell cycle are anergic to restimulation. Anti-CTLA-4 mAb treatment during primary Ag exposure increases cell cycle progression and enhances recall Ag responsiveness; however, simultaneous treatment with rapamycin, an inhibitor of the mammalian target of rapamycin and potent antiproliferative agent, prevents both effects. The data suggest that cell cycle progression plays a primary role in the regulation of recall Ag responsiveness in CD4+ T cells in vivo. CTLA-4 molecules promote clonal anergy development only indirectly by limiting cell cycle progression during the primary response.
AB - CD4+ T cells that undergo multiple rounds of cell division during primary Ag challenge in vivo produce IL-2 on secondary Ag rechallenge, whereas cells that fail to progress through the cell cycle are anergic to restimulation. Anti-CTLA-4 mAb treatment during primary Ag exposure increases cell cycle progression and enhances recall Ag responsiveness; however, simultaneous treatment with rapamycin, an inhibitor of the mammalian target of rapamycin and potent antiproliferative agent, prevents both effects. The data suggest that cell cycle progression plays a primary role in the regulation of recall Ag responsiveness in CD4+ T cells in vivo. CTLA-4 molecules promote clonal anergy development only indirectly by limiting cell cycle progression during the primary response.
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U2 - 10.4049/jimmunol.167.10.5636
DO - 10.4049/jimmunol.167.10.5636
M3 - Article
C2 - 11698435
AN - SCOPUS:0035889885
SN - 0022-1767
VL - 167
SP - 5636
EP - 5644
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -