OX40 costimulates T cells, increases activated T cell longevity, and promot
es memory acquisition. T cells activated in vivo with agonist anti-OX40 and
ovalbumin have a unique pattern of survival and cell division compared to
control cells, but are able to respond to recall Ag equally well. BrdU inco
rporation shows that early cellular division rates of the anti-OX40-treated
and the control groups are similar. Nevertheless, more BrdU(+) Ag-specific
T cells accumulate in lymphoid tissue upon anti-OX40 administration. Thus,
OX40 ligation does not necessarily lead to increased cell cycle entry, but
promotes the accumulation of dividing cells. However, CFSE staining shows
that OX40 ligation allows cells to progress through more cellular division
cycles, while control cells stall or die. Moreover, OX40 ligation leads to
a proportional decrease in apoptotic Ag-specific T cells. Thus, OX40 ligati
on boosts immunity by promoting an increase in the number cell cycles compl
eted, thereby increasing the life span of Ag-activated CD4 T cells, (C) 200
1 Academic Press.