MACROPHAGE PROSTAGLANDIN PRODUCTION CONTRIBUTES TO THE AGE-ASSOCIATEDDECREASE IN T-CELL FUNCTION WHICH IS REVERSED BY THE DIETARY ANTIOXIDANT VITAMIN-E
Aa. Beharka et al., MACROPHAGE PROSTAGLANDIN PRODUCTION CONTRIBUTES TO THE AGE-ASSOCIATEDDECREASE IN T-CELL FUNCTION WHICH IS REVERSED BY THE DIETARY ANTIOXIDANT VITAMIN-E, Mechanism of ageing and development, 93(1-3), 1997, pp. 59-77
The aging process is associated with a decline in T cell-mediated immu
nity, including decreased interleukin (IL)-2 production and mitogen-in
duced T cell proliferation. Because macrophages (M phi) from old mice
have higher production of prostaglandin (PG) E(2) than young mice, and
PGE(2) has been shown to suppress T cell-mediated function, we hypoth
esized that increased production of PGE(2) would contribute to decreas
ed T cell function with aging and that decrease in PGE(2) production b
y dietary antioxidants would enhance T cell-mediated function. Experim
ents were conducted in which combinations of purified M phi and T cell
s (> 95% pure) from young or old C57BL/6NIA mice were cultured togethe
r. Go-cultures containing T cells and M phi from old mice had reduced
ConA-stimulated proliferation and IL-2 secretion than those consisting
of T cells and M phi from young mice. Addition of M phi from old mice
suppressed proliferation and IL-2 secretion by T cells from young mic
e. Likewise, T cells from old mice secreted more IL-2 when cultured wi
th M phi from young mice compared to those cultured with M phi from ol
d mice. Addition of PGE(2), at concentrations produced by old M phi, d
ecreased proliferation and IL-2 production by young but not old T cell
s. Neither addition of H2O2 at physiological levels, nor catalase chan
ged the response of cultures from young or old mice. However, addition
of indomethacin and the antioxidant nutrient vitamin E, both of which
decreased PGE(2) production, improved T cell proliferation and IL-2 p
roduction. These experiments demonstrate that increased production of
PGE(2) by M phi contributes to the age-associated decline in T cell fu
nction. Vitamin E improves T cell responsiveness in old mice mostly by
reducing M phi PGE(2) production, although a direct effect of vitamin
E on T cells was also observed. (C) 1997 Elsevier Science Ireland Ltd
.