Advertisement

Lymphocyte Proliferation, Lymphokine Production, and Lymphocyte Receptors in Aging

  • A. L. De Weck
  • F. Kristensen
  • F. Joncourt
  • F. Bettens
  • G. D. Bonnard
  • Y. Wang
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Lymphocyte proliferation is one of the basic functions of the immune system, since it appears required as well for the acquisition of immunological memory as for clonal expansion of specific lymphocyte populations. In recent years, the combination of several techniques, such as analysis of the cell cycle by cytofluorometry (Darzinkiewicz et al., 1976; Stadler et al., 1980), measurement of [3H]-TdR uptake, detection of membrane receptors by immunofluorescence or ligand binding (Munck and Vira, 1975), and quantitative assessment of various lymphokines produced by proliferating lymphoid cells, has permitted the establishment of an integrated picture of the various events associated with the proliferation of lymphocytes. Although this picture is still fragmentary, the analysis of lymphocyte functions which it makes possible has already been found relevant and informative in several clinical situations, where a dysregulation of lymphocyte functions is apparent. The purpose of this paper is to review briefly the current possibilities to analyze lymphocyte proliferation in clinical situations and their application to the aging process.

Keywords

Lymphocyte Proliferation Human Peripheral Blood Lymphocyte Thymic Hormone Lymphocyte Receptor Murine Spleen Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abrass, I. B., and Scarpace, P. J., 1981, Human lymphocyte betaadrenergic-receptors are unaltered with age, J. Gerontol. 35:329.Google Scholar
  2. Adler, W. H., Jones, K. H., and Brock, M. A., 1978, Aging and immune function, in: The Biology of Aging (J. A. Behnke, C. E. Finch, and G. B. Moment, eds.), p. 221, Plenum Press, New York.CrossRefGoogle Scholar
  3. Bettens, F., Kristensen, F., Walker, C., and de Weck, A. L., 1982, Human lymphocyte proliferation. II. Formation of activated (Gl) cells, Eur. J. Immunol. 12:948–952.PubMedCrossRefGoogle Scholar
  4. Bettens, F., Kristensen, F., Walker, C., Schwulera, U., Bonnard, G. D., and de Weck, A. L., 1983a, Lymphokine regulation of activated (G1) lymphocytes. II. Glucocorticoid and anti-Tac induced inhibition of human T lymphocyte proliferation, J. Immunology, 132:261–265.Google Scholar
  5. Bettens, F., Kristensen, F., Walker, C., Bonnard, G. D., and de Weck, A. L., 1983b, Lymphokine regulation of human lymphocyte proliferation: Formation of resting (GO) cells by removal of interleukin 2 in cultures of proliferating T lymphocytes, Cell Immunol. (in press).Google Scholar
  6. Bonnard, G. D., Yasaka, K., and Jacobson, D., 1979, Ligand-activated T cell growth factor-induced proliferation: Absorption of T cell growth factor by activated T cells, J. Immunol. 123:2704.PubMedGoogle Scholar
  7. Bonnard, G. D., Yasaka, D., and Maca, R. N., 1980, Continued growth of functional T lymphocytes: Production of human T-cell growth factor, Cell. Immunol. 51:390.PubMedCrossRefGoogle Scholar
  8. Bonnard, G. D., Grove, S., and Strong, D. M., 1983, A monoclonal antibody as a potential tool to isolate the human interleukin 2 (IL 2) receptor, in: Roles of Lymphokines and Cytokines in Im-munoregulation (J. J. Oppenheim and S. Cohen, eds.), Academic Press, New York.Google Scholar
  9. Chang, M. P., Makinodan, T., Peterson, W. J., and Strehler, B. L., 1982, Role of T cells and adherent cells in age-related decline in murine interleukin 2 production, J. Immunol. 129:2426.PubMedGoogle Scholar
  10. Crabtree, G., Munck, A., and Smith, K. A., 1980a, Glucocorticoids and lymphocytes. I. Increased glucocorticoid receptor level in antigen-stimulated lymphocytes, J. Immunol. 124:2430.PubMedGoogle Scholar
  11. Crabtree, G., Munck, A., and Smith, K. A., 1980b, Glucocorticoids and lymphocytes. II. Cell-cycle dependent changes in glucocorticoid receptor content, J. Immunol. 125:13.PubMedGoogle Scholar
  12. Darzinkiewicz, Z., Traganos, F., Sharpless, T., and Melamed, M. R., 1976, Lymphocyte stimulation: A rapid multiparameter analysis, Proc. Natl. Acad. Sci. USA 73:2881.CrossRefGoogle Scholar
  13. de Weck, A. L., 1981, Lymphokines and other immunoactive soluble cellular products: Prospects for the future, in: Lymphokines and Thymic Hormones: Their Potential Utilization in Cancer Therapeutics (A. L. Goldstein and M. A. Chirigos, eds.), Raven Press, New York.Google Scholar
  14. Gillis, S., Kozak, R., Durante, M., and Weksler, M. E., 1981, Immunologic studies of aging: Decreased production of and response to T-cell growth factor by lymphocytes from aged humans, J. Clin. Invest. 67:937.PubMedCrossRefGoogle Scholar
  15. Gilman, S. C., Rosenberg, J. S., and Feldman, J. D., 1982, T lymphocytes of young and aged rats. II. Functional defects and the role of interleukin 2, J. Immunol. 126:644.Google Scholar
  16. Good, R. A., West, A. and Fernandes, G., 1980, Nutritional modulation of immune responses, Fed. Proc. 39:3098.PubMedGoogle Scholar
  17. Helderman, J. H., and Strom, T. B., 1979, Role of protein and RNA synthesis in the development of insulin binding sites on activated thymic-derived lymphocytes, J. Biol. Chem. 254:2703.Google Scholar
  18. Joncourt, F., Kristensen, F., and de Weck, A. L., 1981a, Ageing and immunity in outbred NMRI mice: Lack of correlation between age-related decline of the response to T cell mitogens, the antibody response to a T-dependent antigen and lifespan in outbred NMRI mice, Clin. Exp. Immunol. 44:270.Google Scholar
  19. Joncourt, F., Bettens, F., Kristensen, F., and de Weck, A. L., 1981b, Age-related changes of mitogen responsiveness in different lymphoid organs from outbred NMRI mice, Immunobiology 158:39.CrossRefGoogle Scholar
  20. Joncourt, F., Kristensen, F., and de Weck, A. L., 1982a, Age-related changes in G0-G1 transition and proliferative capacity of mitogen-stimulated murine spleen cells, Gerontology 28:281.CrossRefGoogle Scholar
  21. Joncourt, F., Wang, Y., Kristensen, F., and de Weck, A. L., 1982b, Aging and immunity: Decrease in interleukin 2 production and interleukin 2-dependent RNA synthesis in lectin-stimulated murine spleen cells, Immunobiology 163:521.Google Scholar
  22. Joncourt, F., Wang, Y., Kristensen, F., and de Weck, A. L., 1983, Age-related changes in the formation of glucocorticoid and insulin receptors during lectin-induced activation of human peripheral blood lymphocytes, Immunoplogy, in press.Google Scholar
  23. Kay, M. M. B., 1980, Immunological aspects of aging, in: Ageing, Vol. 11 (M. B. Kay, J. E. Galpin, and T. Makinodan, eds.), Raven Press, New York.Google Scholar
  24. Koponen, M., Glieder, A., and Loor, F., 1982, The effects of cyclosporins on the cell cycle of T lymphoid cell lines, Exp. Cell. Res. 140:237.PubMedCrossRefGoogle Scholar
  25. Kristensen, F., and de Weck, A. L., 1982, Use of cytofluorometric techniques for assay of cell cycle regulating lymphokines, in: Human Lymphokines: The Biological Immune Response Modifiers (A. Khan and N. O. Hill, eds.), Academic Press, New York.Google Scholar
  26. Kristensen, F., Joncourt, F., and de Weck, A. L., 1981, The influence of serum on lymphocyte cultures. II. Cell cycle specificity of serum action in spleen cells, Scand. J. Immunol. 14:121.PubMedCrossRefGoogle Scholar
  27. Kristensen, F., Walker, C., Joncourt, F., Bettens, F., and de Weck, A. L., 1982a, Human lymphocyte proliferation. I. Correlation between activated and proliferating T lymphocytes, Immunol. Lett. 5:59.CrossRefGoogle Scholar
  28. Kristensen, F., Walker, C., Bettens, F., Joncourt, F., and de Weck, A. L., 1982b, Assessment of IL 1 and IL 2 effects on cyclng and noncycling murine thymocytes, Cell. Immunol. 74:140.CrossRefGoogle Scholar
  29. Kristensen, F., Bettens, F., Walker, C., Joncourt, F., and de Weck, A. L., 1983, Relationship between cell cycle events and interleukin 2 (IL 2) production, in: Role of Lymphokines and Cytokines in Immunoregulation (J. J. Oppenheim and S. Cohen, eds.), Academic Press, New York.Google Scholar
  30. Krug, U., Krug, F., and Cuatrecasas, P., 1972, Emergence of insulin receptors on human lymphocytes during in vitro transformation, Proc. Natl. Acad. Sci. USA 69:2604.PubMedCrossRefGoogle Scholar
  31. Lakatta, E. G., 1980, Age-related alterations in the cardiovascular response to adrenergic mediated stress, Fed. Proc. 39:3173.PubMedGoogle Scholar
  32. Landman, R., Bittiger, H., and Bühler, F. R., 1981, High affinity beta-2-adrenergic receptors in mononuclear leucocytes: Similar density in young and old normal subjects, Life Sci. 29:1761.CrossRefGoogle Scholar
  33. Leonard, W. J., Depper, J. M., Uchiyama, T., Smith, K. A., Waldmann, T. A., and Green, W. C., 1982, A monoclonal antibody that appears to recognize the receptor for human T cell growth factor: Partial characterization of the receptor, Nature (London) 300:267.CrossRefGoogle Scholar
  34. Makinodan, T., and Kay, M. B., 1980, Age influence on the immune system, Adv. Immunol. 29:287.PubMedCrossRefGoogle Scholar
  35. Masoro, E. J., Yu, B. P., Bertrand, H. A., and Lynd, F. T., 1980, Nutritional probe of the aging process, Fed. Proc. 39:3178.PubMedGoogle Scholar
  36. Miyawaka, T., Yachi, A., Uwadana, N., Ohzeki, S., Nagaoki, T., and Taniguchi, N., 1982, Functional significance of Tac antigen expressed on activated human T lymphocytes: Tac antigen interacts with T cell growth factor in cellular proliferation, J. Immunol. 129:2474.Google Scholar
  37. Munck, A., and Vira, C., 1975, Methods for assessing hormone-receptor kinetics with cells in suspension: Receptor bound and nonspecific bound hormone; cytoplasmic nuclear translocation, Methods Enzymol. 36:255.PubMedCrossRefGoogle Scholar
  38. Pardee, A. B., Dubrow, R., Hamlin, H. L., and Kletzren, R. F., 1978, Animal cell cycle, Annu. Rev. Biochem. 47:715.PubMedCrossRefGoogle Scholar
  39. Robb, R. J., Munck, A., and Smith, K. A., 1981, T cell growth factor receptors: Quantitation, specificity and biological relevance, J. Exp. Med. 154:1455.PubMedCrossRefGoogle Scholar
  40. Roth, G. S., 1979, Hormone receptor changes during adulthood and senescence: Significance for aging research, Fed. Proc. 38:1910.PubMedGoogle Scholar
  41. Sartin, J., Chaudhuri, M., Obenrader, M., and Adelman, R. C., 1980, The role of hormones in changing adaptive mechanisms during aging, Fed. Proc. 39:3163.PubMedGoogle Scholar
  42. Slauson, D. O., Walker, C., Kristensen, F., Wang, Y., and de Weck, A. L., 1983, Mechanisms of serotonin-induced lymphocyte proliferation inhibition, Cell. Immunol. in press.Google Scholar
  43. Smith, K. A., 1980, T cell growth factor, Immunol. Rev. 51:337.PubMedCrossRefGoogle Scholar
  44. Smith, K. A., Lachman, L. B., Oppenheim, J. J., and Favata, M. F., 1980, The functional relationship of the interleukins, J. Exp. Med. 151:1551.PubMedCrossRefGoogle Scholar
  45. Stadler, B. M., Kristensen, F., and de Weck, A. L., 1980, Thymocyte activation by cytokines: Direct assessment of G0-G1 transition by flow cytometry. Cell. Immunol. 55:436.PubMedCrossRefGoogle Scholar
  46. Stadler, B. M., Dougherty, S., Farrar, J. J., and Oppenheim, J. J., 1981, Relationship of cell cycle to recovery of IL 2 activity from human mononuclear cells, human and mouse T cell lines, J. Immunol. 127:1936.PubMedGoogle Scholar
  47. Thoman, M. L., and Weigle, W. O., 1981, Lymphokines and aging: Interleukin 2 production and activity in aged animals, J. Immunol. 127:2102.PubMedGoogle Scholar
  48. Thoman, M. L., and Weigle, W. O., 1982, Cell-mediated immunity in aged mice: An underlying lesion in IL 2 synthesis, J. Immunol. 128:2358.PubMedGoogle Scholar
  49. Uchiyama, T., Broder, S., and Waldman, T. A., 1981, A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells, J. Immunol. 126:1393.PubMedGoogle Scholar
  50. Walford, R. L., Liu, R. K., Gerbase-Delima, M., Mathies, M., and Smith, G. S., 1973, Longterm dietary restriction and immune function in mice: Response to sheep red blood cells and to mitogenic agents, Mech. Ageing Dev 2:447.PubMedCrossRefGoogle Scholar
  51. Walker, C., Kristensen, F., Bettens, F., and de Weck, A. L., 1983, Lymphokine regulation of activated (Gl) cells. I. Prostaglandin E2 induced inhibition of interleukin 2 production, J. Immunol. 130:1770.PubMedGoogle Scholar
  52. Wang, Y., Joncourt, F., Kristensen, F., and de Weck, A. L., 1983a, Cell cycle-related changes in number of T-lymphocyte receptors for glucocorticoids and insulin, Int. J. Immunopharmacol. Google Scholar
  53. Wang, Y., Kristensen, F., Joncourt, F., Slauson, D. O., and de Weck, A. L., 1983b, Analysis of 3H-histamine interaction with lymphocytes: Receptor or uptake?, Clin. Exp. Immunol. 54:501.PubMedGoogle Scholar
  54. Weksler, M. E., 1981, the senescence of the immune system, Hosp. Prac. October, p. 53.Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • A. L. De Weck
    • 1
  • F. Kristensen
    • 1
  • F. Joncourt
    • 1
  • F. Bettens
    • 1
  • G. D. Bonnard
    • 1
  • Y. Wang
    • 1
  1. 1.Institute for Clinical Immunology, InselspitalUniversity of BernBernSwitzerland

Personalised recommendations