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Analysis of the Ability of Spleen Cells from Aged Mice to Produce Allospecific Cytotoxic Cells

  • Susan R. S. Gottesman
  • J. M. Edington
Conference paper
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

The ability of aged rodents and humans to respond to foreign antigenic challenge decreases with age (Makinodan, 1977; Gottesman, 1987). This age-related deficiency is particularly severe in the T-cell system, as evidenced by the involution of the thymus, the decline in T- proliferative response to mitogens and specific antigens (Meredith and Walford, 1977; Miller and Stutman, 1981), the defeat in the ability to generate specific T-suppressor cells (Gottesman et al., 1984; Yin et al., 1988), and the inability of T cells to provide help for antibody production and cell-mediated immune responses (Miller and Stutman, 1981; Zharhary et al., 1984). Although many of these defects are contributed to by reduced lymphokine production by cells from aged donors (Miller and Stutman, 1981; Thoman and Weigle, 1982; Chang et al., 1982; Gilman et al., 1982), these activities are not all totally restored by addition of exogenous lymphokines (Gottesman et al., 1985). Cytotoxic T-lymphocyte (CTL) activity, a vital function for survival of the organism, shows an age-related decrease when assayed in bulk cultures (Gottesman et al., 1981). Limiting dilution analysis show a deficiency in a proportion of aged mice tested in CTL precursor frequency, under conditions in which helper cell function and interleukin-2 (IL-2) production are not limiting (Miller, 1984; Gorczynski and Chang, 1984; Zharhary et al., 1984).

Keywords

Spleen Cell Aged Mouse Young Mouse Young Control Mixed Lymphocyte Culture 
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.

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References

  1. Chang, M., 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: 2426–2430.PubMedGoogle Scholar
  2. 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 128: 644–650.PubMedGoogle Scholar
  3. Gorczynski, R. M., and Chang, M.-P., 1984, Peripheral (somatic) expansion of the murine cytotoxic T lymphocyte repertoire. II. Comparison of diversity in recognition repertoire of alloreactive T cells in spleen and thymus of young or aged DBA/2J mice transplanted with bone marrow cells from young or aged donors, J. Immunol. 133: 2381–2389.PubMedGoogle Scholar
  4. Gottesman, S. R. S., 1987, T cell function in aging—An update, in: Review of Biological Research in Aging, Vol. 3 ( W. H. Adler, ed.), Liss, New York, pp. 95–110.Google Scholar
  5. Gottesman, S. R. S., Kristie, J. A., and Walford, R. L., 1981, Proliferative and cytotoxic immune functions in aging mice. I. Sequence of decline of reactivities measured under optimal and suboptimal sensitization conditions, Immunology 44: 607–616.PubMedGoogle Scholar
  6. Gottesman, S. R. S., Walford, R. L., and Thorbecke, G. J., 1984, Proliferative and cytotoxic immune functions in aging mice. II. Decreased generation of specific suppressor cells in alloreactive cultures, J. Immunol. 133: 1782–1787.PubMedGoogle Scholar
  7. Gottesman, S. R. S., Walford, R. L., and Thorbecke, G. J., 1985, Proliferative and cytotoxic immune functions in aging mice. III. Exogenous interleukin-2 rich supernatant only partially restores alloreactivity in vitro, Mech. Aging Dev. 31: 103–113.PubMedCrossRefGoogle Scholar
  8. Grimm, E. A., and Bonavida, B., 1977, Studies on the induction and expression of T cell mediated immunity. VI. Heterogeneity of lytic efficiency exhibited by isolated cytotoxic T lymphocytes prepared from highly enriched populations of effector-target conjugates, J. Immunol. 119: 1041–1047.PubMedGoogle Scholar
  9. Makinodan, T., 1977, Immunity and Aging, in: Handbook of the Biology of Aging ( C. E. Finch and L. Hayflick, eds.), Von Nostrand-Reinhold, New York, pp. 379–408.Google Scholar
  10. Meredith, P., and Walford, R., 1977, Effect of age on response to T- and B-mitogens in mice congenic at the H-2 locus, Immunogenetics 5: 109–128.CrossRefGoogle Scholar
  11. Miller, R. A., 1984, Age-associated decline in precursor frequency for different T cell-mediated reactions, with preservation of helper or cytotoxic effect per precursor cell, J. Immunol. 132: 63–68.PubMedGoogle Scholar
  12. Miller, R. A., and Stutman, O., 1981, Decline, in aging mice, of the anti-2,4,6-trinitrophenyl (TNP) cytotoxic T cell response attributable to loss of Lyt-2 interleukin 2-producing helper cell function, Eur. J. Immunol. 11: 751–756.PubMedCrossRefGoogle Scholar
  13. Thoman, M. L., and Weigle, W. O., 1982, Cell mediated immunity in aged mice: An underlying lesion in IL-2 synthesis, J. Immunol. 128: 2358–2361.PubMedGoogle Scholar
  14. Yin, J. -Z., Gottesman, S. R. S., Bell, M. K., and Thorbecke, G. J., 1988, Resistance to low dose tolerance and enhanced antibody repsonses of aged as compared to young mice immunized with pneumococca; polysaccharides, Aging: Immunology and Infectious Disease 1: 131.Google Scholar
  15. Zagury, D., Bernard, J., Thierness, N., Feldman, M., and Berke, G., 1975, Isolation and characterization of individual functionally reactive cytotoxic T lymphocytes: Conjugation, killing, and recycling at the single cell level, Eur. J. Immunol. 5: 818–822.CrossRefGoogle Scholar
  16. Zharhary, D., Segev, Y., and Gershon, H. E., 1984, T-cell cytotoxicity and aging: Differing causes of reduced response in individual mice, Mech. Aging Dev. 25: 129–140.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Susan R. S. Gottesman
    • 1
  • J. M. Edington
    • 1
  1. 1.Department of PathologyNew York University Medical CenterNew YorkUSA

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