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Macrophage prostaglandin production contributes to the age-associated decrease in T cell function which is reversed
1Nutritional Immunology Laboratory, Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Abstract:
The aging process is associated with a decline in T cell-mediated immunity, including decreased interleukin (IL)-2 production and mitogen-induced T cell proliferation. Because macrophages (M phi) from old mice have higher production of prostaglandin (PG) E2 than young mice, and PGE2 has been shown to suppress T cell-mediated function, we hypothesized that increased production of PGE2 would contribute to decreased T cell function with aging and that decrease in PGE2 production by dietary antioxidants would enhance T cell-mediated function. Experiments were conducted in which combinations of purified M phi and T cells (> 95% pure) from young or old C57BL/6N1A mice were cultured together. Co-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 mice. Likewise, T cells from old mice secreted more IL-2 when cultured with M phi from young mice compared to those cultured with M phi from old mice. Addition of PGE2, at concentrations produced by old M phi, decreased proliferation and IL-2 production by young but not old T cells. Neither addition of H2O2 at physiological levels, nor catalase changed the response of cultures from young or old mice. However, addition of indomethacin and the antioxidant nutrient vitamin E, both of which decreased PGE2 production, improved T cell proliferation and IL-2 production. These experiments demonstrate that increased production of PGE2 by M phi contributes to the age-associated decline in T cell function. Vitamin E improves T cell responsiveness in old mice mostly by reducing M phi PGE2 production, although a direct effect of vitamin E on T cells was also observed.
Insights
Aging impairs T cell immunity, partly due to increased prostaglandin E2 (PGE2) from macrophages. Antioxidants like vitamin E reduce PGE2, enhancing T cell function in older mice.
Area of Science:
- Immunology
- Aging Research
- Cellular Biology
Background:
- Aging is linked to reduced T cell immunity, evidenced by lower interleukin-2 (IL-2) production and proliferation.
- Macrophages (M phi) from aged mice produce more prostaglandin E2 (PGE2), a known suppressor of T cell functions.
Purpose of the Study:
- To investigate the hypothesis that elevated PGE2 contributes to age-related T cell dysfunction.
- To determine if reducing PGE2 production with dietary antioxidants can restore T cell function in aging.
Main Methods:
- Co-culturing purified T cells and macrophages (M phi) from young and old C57BL/6N1A mice.
- Assessing T cell proliferation and IL-2 secretion in response to Concanavalin A (ConA).
- Evaluating the effects of adding PGE2, hydrogen peroxide (H2O2), catalase, indomethacin, and vitamin E on T cell cultures.
Main Results:
- Co-cultures with M phi from old mice showed reduced T cell proliferation and IL-2 secretion compared to young mice.
- Exogenous PGE2 suppressed T cell responses in young but not old mice.
- Indomethacin and vitamin E, which reduced PGE2 production, significantly improved T cell proliferation and IL-2 secretion.
Conclusions:
- Increased PGE2 production by macrophages is a key factor in age-associated decline of T cell-mediated immunity.
- Vitamin E enhances T cell responsiveness in aged mice primarily by decreasing M phi PGE2 production, with a potential direct effect on T cells also noted.