Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors.

Using cDNA probes to human interleukin 2 (IL2) and interleukin 2 receptor (IL2R), the amount of IL2 and IL2R mRNA produced by PHA stimulated peripheral blood mononuclear cells from young (less than 40 yr) and old (greater than 60 yr) donors was quantitated. Stimulated cell cultures from each individual were also examined for proliferative ability, expression of membrane IL2R, membrane IL2R density, and for the amount of IL2R shed into the culture supernatant. Induction of IL2 and IL2R mRNAs were decreased in cells from elderly individuals, as were the levels of IL2 secretion, the percentage of IL2R+ T cells and the density of membrane IL2R per cell. The results suggest that decreased expression of both IL2 and IL2R mRNA contributes to the low synthesis of IL2 and membrane IL2R, respectively, and is partially responsible for the diminished proliferative activity observed in lymphocytes from the elderly.

[1]  W. Leonard,et al.  The IL-2 receptor beta chain (p70): role in mediating signals for LAK, NK, and proliferative activities. , 1987, Science.

[2]  W. Greene The human interleukin-2 receptor: a molecular and biochemical analysis of structure and function. , 1987, Clinical research.

[3]  W. Chan,et al.  The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[4]  B. Cullen,et al.  A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors , 1987, Nature.

[5]  W. Greene,et al.  Interleukin 2 binding molecule distinct from the Tac protein: analysis of its role in formation of high-affinity receptors. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[6]  W. Greene,et al.  Internalization of interleukin 2 is mediated by the beta chain of the high-affinity interleukin 2 receptor , 1987, The Journal of experimental medicine.

[7]  A. Kumar,et al.  Evidence for negative regulation of T cell growth by low affinity interleukin 2 receptors. , 1987, Journal of immunology.

[8]  G. Jay,et al.  The released interleukin 2 receptor binds interleukin 2 efficiently. , 1986, Journal of immunology.

[9]  T. Waldmann,et al.  Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[10]  T. Diamantstein,et al.  Regulation of interleukin-2 receptor expression and receptor release. , 1986, Molecular immunology.

[11]  P. Nowell,et al.  The role of the accessory cell in mitogen-stimulated human T cell gene expression. , 1986, Journal of immunology.

[12]  M. Pahlavani,et al.  The effect of aging on the expression of interleukin 2 messenger ribonucleic acid. , 1986, Cellular immunology.

[13]  H. Vié,et al.  Decline, with age, in the proportion of mouse T cells that express IL-2 receptors after mitogen stimulation , 1986, Mechanisms of Ageing and Development.

[14]  D. Nelson,et al.  Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. , 1985, Journal of immunology.

[15]  W. Leonard,et al.  Sequential expression of genes involved in human T lymphocyte growth and differentiation , 1985, The Journal of experimental medicine.

[16]  M. Thoman,et al.  Reconstitution of in vivo cell-mediated lympholysis responses in aged mice with interleukin 2. , 1985, Journal of immunology.

[17]  D. Cantrell,et al.  Interleukin 2 regulates its own receptors. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[18]  K. Ratheiser,et al.  Lack of correlation between serum cholesterol levels, lymphocyte plasma membrane fluidity and mitogen responsiveness in young and aged chickens , 1984, Mechanisms of Ageing and Development.

[19]  G. Crabtree,et al.  Molecular cloning and expression of cDNAs for the human interleukin-2 receptor , 1984, Nature.

[20]  S. Arya,et al.  Dexamethasone-mediated inhibition of human T cell growth factor and gamma-interferon messenger RNA. , 1984, Journal of immunology.

[21]  D. Cantrell,et al.  The interleukin-2 T-cell system: a new cell growth model. , 1984, Science.

[22]  M. Melamed,et al.  Immunological studies of aging. IX. Impaired proliferation of T lymphocytes detected in elderly humans by flow cytometry. , 1984, Journal of immunology.

[23]  G. Crabtree,et al.  T-cell growth factor: complete nucleotide sequence and organization of the gene in normal and malignant cells. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[24]  E. Reinherz,et al.  Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Innes,et al.  Induction of DNA synthesis in isolated nuclei by cytoplasmic factors. II. Normal generation of cytoplasmic stimulatory factors by lymphocytes from aged humans with depressed proliferative responses. , 1984, Journal of immunology.

[26]  D. Cantrell,et al.  Transient expression of interleukin 2 receptors. Consequences for T cell growth , 1983, The Journal of experimental medicine.

[27]  J. Nagel,et al.  Mitogenic activity of 12-O-tetradecanoyl phorbol-13-acetate on peripheral blood lymphocytes from young and aged adults. , 1982, Clinical and experimental immunology.

[28]  M. Thoman,et al.  Cell-mediated immunity in aged mice: an underlying lesion in IL 2 synthesis. , 1982, Journal of immunology.

[29]  S. Gilman,et al.  T lymphocytes of young and aged rats. II. Functional defects and the role of interleukin-2. , 1982, Journal of immunology.

[30]  J. Nagel,et al.  Enumeration of T lymphocyte subsets by monoclonal antibodies in young and aged humans. , 1981, Journal of immunology.

[31]  D. Hegner Age-dependence of molecular and functional changes in biological membrane properties , 1980, Mechanisms of Ageing and Development.

[32]  P. Thomas,et al.  Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[33]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[34]  Kendall A. Smith,et al.  T cell growth factor: parameters of production and a quantitative microassay for activity. , 1978, Journal of immunology.

[35]  C. F. Lange Immunology of Aging , 2019, Frontiers Research Topics.

[36]  J. Nagel,et al.  Monoclonal antibody analysis of T-lymphocyte subsets in young and aged adults. , 1983, Immunological communications.

[37]  H. Blau,et al.  Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed , 1983, Molecular and cellular biology.