T Cell Differentiation and Functional Maturation in Aging Mice

  • Marilyn L. Thoman
  • D. N. Ernst
  • M. V. Hobbs
  • W. O. Weigle
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 330)


Advancing age is accompanied by changes in immune potential, frequently characterized as declines in the capacity to mount effective cell-mediated or humoral immune responses (reviewed in 1–3). Age-related functional changes can be identified earliest in the T cell compartment, therefore understanding the impact of advancing age on T cell activity may provide the key to understanding immune senescence. The expression of effector function by T cells requires their activation to cell cycle entry. The sequence of events involved in T cell activation are affected by the aging process and result in the altered T cell reactivity demonstrated in the aged.


Spleen Cell Phorbol Myristate Acetate Aged Mouse Aged Animal Phorbol Myristate Acetate 
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  1. 1.
    Nagel, J.E. Rev. Biol. Res. Aging 1:103 (1983).Google Scholar
  2. 2.
    Miller, R. A. The cell biology of aging: immunological models. J. Geron. 44: B4 (1989).CrossRefGoogle Scholar
  3. 3.
    Thoman, M. L. and Weigle, W. O. The cellular and subcellular bases of immunosenescence. Adv. Immunol. 46:221 (1989).PubMedCrossRefGoogle Scholar
  4. 4.
    Isakov, N., Mally, M. I., Scholz, W. and Altman, A. T-lymphocyte activation: The role of protein kinase C and the bifurcating inositol phospholipid signal transduction pathway. Immunol. Rev. 95:89 (1989).CrossRefGoogle Scholar
  5. 5.
    Linch, D. C., Wallace, D. L. and O’Flynn, K. Signal transduction in human T lymphocytes. Immunol Rev. 95:137 (1987).PubMedCrossRefGoogle Scholar
  6. 6.
    Cantrell, D. and Smith, K. A. The interleukin-2 T-cell systenr.A new cell growth model. Science 224:1312 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    Thoman, M. L. and Weigle, W. O. Partial restoration of ConA-induced proliferation, IL-2 receptor expression and IL-2 synthesis in aged murine lymphocytes by phorbol myristate acetate and ionomycin. Cell. Immunol. 114:1 (1988).PubMedCrossRefGoogle Scholar
  8. 8.
    Miller, R. A., Jacobson, B., Weil, G. and Simons, E. R. Diminished calcium in-flux in lectin stimulated T cells from old mice. J. Cell. Physiol. 132:337 (1987).PubMedCrossRefGoogle Scholar
  9. 9.
    Lerner, A., Philosophe, B. and Miller, R. Defective calcium influx and preserved inositol phosphate generation in T cells from old mice. Aging: Imunol. Infect. Dis. 1:149 (1988).Google Scholar
  10. 10.
    Prouse, J., Filburn, C., Harrison, S., Bucholz, N. and Nordin, A. Agerelated defect in signal transduction during lectin activation of murine T lymphocytes. J. Immunol. 139:1472 (1987).Google Scholar
  11. 11.
    Ernst, D.N., Weigle, W.O., McQuitty, D.N., Rothermel, A.L. and Hobbs, M.V. Stimulation of murine T cell subsets with anti-CD3 antibody. Age-related fects in the expression of early activation molecules. J. Immunol. 142:1413 (1989).PubMedGoogle Scholar
  12. 12.
    Neckers, L. M. and Cossman, J. Transferrin receptor induction in mitogenstimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc. Natl. Acacl. Sci. USA. 80:3493 (1983).Google Scholar
  13. 13.
    Herzberg, V. L. and Smith, K. A. T cell growth without serum. J. Immunol. 139:998 (1987).PubMedGoogle Scholar
  14. 14.
    Stutman, O. Lymphocyte subpopulations in NZB mice: Deficit of thymusdependent lymphocytes. J. Immunol. 109:602 (1972).PubMedGoogle Scholar
  15. 15.
    Callard, R. E. and Basten, A. Immune function in aged mice. I. T-cell responsiveness using phytohaemagglutinin as a functional probe. Cell. Immunol. 31:13 (1977).PubMedCrossRefGoogle Scholar
  16. 16.
    O’Leary, J. J., Fox, R., Bergh, N., Rodysill, K. and Hallgren, H. M. Expression of the human T cell antigen receptor complex in advanced age. Mech. Age. Dev. 45:239 (1988).CrossRefGoogle Scholar
  17. 17.
    Sidman, C. L., Luther, E. A., Marshall, J. D., Nguyen, K. A., Roopenian, D. C. and Worthen, S. M. Increased expression of major histocompatibility complex antigens on lymphocytes from aged mice. Proc. Natl Acad. Sci. USA. 84:7624 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    Mosmann, T., Cherwinski, H., Bond, M., Giedlin, M. and Coffman, R. Two types of murine helper T cell clone 1. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136:2348 (1986).PubMedGoogle Scholar
  19. 19.
    Mosmann, T. and Coffman, R. Heterogeneity of cytokine secretion patterns and function of helper T cells. Adv. Immunol. 46:111 (1989).PubMedCrossRefGoogle Scholar
  20. 20.
    Hayakawa, K. and Hardy, R. Murine CD4+T cell subsets defined. J. Exp. Med. 168:1825 (1988).PubMedCrossRefGoogle Scholar
  21. 21.
    Bottomley, K., Lugman, M., Greenbaum, L., Carding, S., West, J., Pasqualini, T. and Murphy, D. A monoclonal antibody to murine CD45R distinguishes CD4+T cell populations that produce different cytokines. Eur. J. Immunol. 19:617 (1989).CrossRefGoogle Scholar
  22. 22.
    Birkeland, M. L., Johnson, P., Trowbridge, I. S. and Pure, E. Changes in CD45 isoform expression accompany antigen-induced murine T-cell activation. Proc. Natl Acad. Sci. USA. 86:6734 (1989).PubMedCrossRefGoogle Scholar
  23. 23.
    Lee, W. T., Yin, X. M. and Vitetta, E. S. Functional ontogenetic analysis of murine CD45Rhi and CD45R10CD4+T cells. J. Immunol. 144:3288 (1990).PubMedGoogle Scholar
  24. 24.
    Butterfield, K., Fathman, G. and Budd, R. A subset of memory CD4+ helper T lymphocytes identified by expression of Pgp-1. J. Exp. Med. 169:1461 (1989).PubMedCrossRefGoogle Scholar
  25. 25.
    MacDonald, H. R., Budd, R. C. and Cerotini, J.-C. Pgp-1 (Ly24) as a marker of murine memory T lymphocytes. Curr. Top. Microbiol. Immunol. 159:97 (1990).PubMedCrossRefGoogle Scholar
  26. 26.
    Ceredig, R., Lowenthal, J., Nabholz, M. and MacDonald, H. Expression of interleukin 2 receptors as a differentiation marker on intrathymic stem cells. Nature 314:98 (1985).PubMedCrossRefGoogle Scholar
  27. 27.
    Dialynas, D. P., Wilde, D. B., Marrack, P., Pierres, A., Wall, K. A., Havran, W., Otten, G., Loken, M. R., Pierres, M., Kappler, J. and Fitch, F. W. Characterization of the murine antigenic determinant designated L3T4A, recognized by monoclonal antibody GK1.5:expression of L3T4A, by functional T cell clones appears to correlate primarily with class II MHC antigenreactivity. Immunol. Rev. 74:1983 (1983).CrossRefGoogle Scholar
  28. 28.
    Sarimento, M., Glasebrook, A. and Fitch, F. W. IgG or IgM monoclonal antibodies reactive with different determinants of the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J. Immunol. 125:2665 (1980).Google Scholar
  29. 29.
    Trowbridge, I. S., Lesley, J., Schulte, R., Hyman, R. and Trotter, J. Biochemical characterizaton and cellular distribution of a polymorphic murine cell-surface glycoprotein expressed on lymphoid cells. Immunogenetics 15:299 (1982).PubMedCrossRefGoogle Scholar
  30. 30.
    Ernst, D. N., Hobbs, M. V., Torbett, B. E., Glasebrook, A. L., Rehse, M. A., Bottomly, K., Hayakawa, K., Hardy, R. A. and Weigle, W. O. Differences in the expression profiles of CD45RB, Pgp-1, and 3G11 membrane antigens and in the patterns of lymphokine secretion by splenic CD4+T cells from young and aged mice. J. Immunol. in press (1990).Google Scholar
  31. 31.
    Scollay, R., Butcher, E. and Weissman, I. Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur. J. Immunol. 10:210 (1980).PubMedCrossRefGoogle Scholar
  32. 32.
    Lerner, A., Yamada, T., Miller, R. Pgp-lhi T lymphocytes accumulate with age in mice and respond poorly to concanavalin A. Eur. J. Immunol. 19:977 (1989).PubMedCrossRefGoogle Scholar
  33. 33.
    Thoman, M. L. and Weigle, W. O. Lymphokines and aging:lnterleukin-2 production and activity in aged animals. J. Immunol. 127:2102 (1981).PubMedGoogle Scholar
  34. 34.
    Thoman, M. L. and Weigle, W. O. Cell-mediated immunity in aged mice: an underlying lesion in IL-2 synthesis. J. Immunol. 128:2358 (1982).PubMedGoogle Scholar
  35. 35.
    Thoman, M. L. and Weigle, W. O. Deficiency in suppressor T (fell activity in aged animals. Reconstitution of this activity by Interleukin 2. J. Exp. Med. 157:2184 (1983).PubMedCrossRefGoogle Scholar
  36. 36.
    Thoman, M. L. and Weigle, W. O. Reconstitution of in vivo cell-mediated lympholysis responses in aged mice with Interleukin 2. J. Immunol. 134:949 (1985).PubMedGoogle Scholar
  37. 37.
    Tosi, P., Kraft, R., Luzi, P., Cintorino, M., Fankhauser, G., Hess, M. and Coltier, H. Involution patterns of the human thymus. I. Size of the cortical area as a function of age. Clin. Exp. Immunol. 47:497 (1982).PubMedGoogle Scholar
  38. 38.
    Weksler, M. The thymus gland and aging. Ann. Intern. Med. 98:105 (1988).Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Marilyn L. Thoman
    • 1
  • D. N. Ernst
    • 1
  • M. V. Hobbs
    • 1
  • W. O. Weigle
    • 1
  1. 1.Department of ImmunologyResearch Institute of Scripps ClinicLa JollaUSA

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