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Age-associated decline in IL-4 production by murine T lymphocytes in extended culture
1Institute of Gerontology, University of Michigan, Ann Arbor.
Aging leads to an increase in the proportion of cells that have the surface phenotype (CD45RBlo, CD44hi) characteristic of memory T lymphocytes and also to a decline in both the production of IL-2 and the response to this lymphokine. Several groups have reported an increase, with age, in the secretion of IL-4 in short-term T cell cultures and have suggested that this increase could reflect the age-dependent accumulation of memory T cells, which are thought to be principally responsible for IL-4 production in young mice. Because the response to IL-2 declines with age, we hypothesized that IL-4 production would also decline with age if tested under conditions that promoted IL-2-driven expansion and maturation of IL-4-secreting effectors. Using a culture system in which T cells are first activated by immobilized anti-CD3 antibody for 2 days, and then cultured with anti-CD3 plus IL-2 for an additional 9-11 days, we found a 3-fold decline with age in IL-4 production by murine splenic CD4 T cells. Under these conditions memory (CD45RBlo) CD4 T cells from young mice produced 22-fold more IL-4 than the reciprocal naive (CD44lo) subset. Production of IL-4 by old T cells was also largely attributable to memory T cells, but memory cells from these old donors generated 6-fold less IL-4 in extended cultures than memory cells from young donors. Cultured memory (but not naive) T cells increase in number over a 9-day interval, but the amount of expansion by young memory cells is 4-fold higher than that for old cells. We conclude that the production of IL-4 by memory T cells declines with age under conditions that promote IL-2-driven proliferation and differentiation.
Aging leads to an increase in the proportion of cells that have the surface phenotype (CD45RBlo, CD44hi) characteristic of memory T lymphocytes and also to a decline in both the production of IL-2 and the response to this lymphokine. Several groups have reported an increase, with age, in the secretion of IL-4 in short-term T cell cultures and have suggested that this increase could reflect the age-dependent accumulation of memory T cells, which are thought to be principally responsible for IL-4 production in young mice. Because the response to IL-2 declines with age, we hypothesized that IL-4 production would also decline with age if tested under conditions that promoted IL-2-driven expansion and maturation of IL-4-secreting effectors. Using a culture system in which T cells are first activated by immobilized anti-CD3 antibody for 2 days, and then cultured with anti-CD3 plus IL-2 for an additional 9-11 days, we found a 3-fold decline with age in IL-4 production by murine splenic CD4 T cells. Under these conditions memory (CD45RBlo) CD4 T cells from young mice produced 22-fold more IL-4 than the reciprocal naive (CD44lo) subset. Production of IL-4 by old T cells was also largely attributable to memory T cells, but memory cells from these old donors generated 6-fold less IL-4 in extended cultures than memory cells from young donors. Cultured memory (but not naive) T cells increase in number over a 9-day interval, but the amount of expansion by young memory cells is 4-fold higher than that for old cells. We conclude that the production of IL-4 by memory T cells declines with age under conditions that promote IL-2-driven proliferation and differentiation.