Interleukin 2, interleukin 2 receptor, and interferon-gamma synthesis and mRNA expression in phorbol myristate acetate and calcium ionophore A23187-stimulated T cells from elderly humans.
The levels of interleukin 2 (IL-2), interleukin 2 receptor (IL-2R), and interferon-gamma (IFN-gamma) specific mRNA and their gene products were examined in phorbol myristate acetate (PMA) and calcium ionophore A23187-costimulated purified T cells from young and elderly humans. In addition, the number of high-affinity IL-2R per activated cell, the high-affinity IL-2R density, and the proliferative response of the cells were measured. Among PMA/A23187-stimulated T cells, there was no statistically significant age-related difference in IL-2 or IL-2R specific mRNA accumulation or in the amount of IL-2 or IL-2R synthesized. IFN-gamma specific mRNA was increased significantly in T cells from elderly individuals and the amount of IFN-gamma synthesized by PMA/A23187-activated T cells was nearly double that produced by cells from young individuals. Quantification of the number of high-affinity IL-2R by [125I]IL-2 binding demonstrated there was no decrease in either the mean number or the dissociation constant of the high-affinity IL-2R on activated T cells of the elderly. Despite producing large amounts of IL-2 and having comparable numbers of both low- and high-affinity IL-2R. PMA/A23187-stimulated T cells from elderly subjects still proliferated less vigorously than did T cells from young persons. The addition of exogenous IL-2 to the cultured cells did not fully correct this age difference. Our findings that the expression of the IL-2, IL-2R, and IFN-gamma genes are not constitutionally defective in the elderly support the hypothesis that the age-related decline in proliferation observed in mitogen-stimulated T cells of the elderly is most likely attributable to alterations in the transmission of signals from the cell membrane to the nucleus.
Chopra
R K
RK
Clinical Immunology Section, National Institute on Aging, Baltimore, Maryland 21224.
Holbrook
N J
NJ
Powers
D C
DC
McCoy
M T
MT
Adler
W H
WH
Nagel
J E
JE
D000328:Adult; D000368:Aged; D000375:Aging; D000001:Calcimycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D000001:Calcimycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate