Characterization of Lithium Effects on Two Aspects of T-Cell Function

  • E. W. Gelfand
  • R. Cheung
  • D. Hastings
  • H.-M. Dosch
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 127)


There is increasing evidence that positive and negative feedback control mechanisms regulate the immune response. At the molecular level, candidates for these regulatory effects are the cyclic nucleotides. Although most of the studies demonstrating a role for these compounds have involved non-lymphoid tissues, cyclic nucleotides also appear to be important mediators in the regulation of a variety of specific lymphocyte functions. These functions include triggering of differentiation, expression of discrete receptor activities, lymphocyte proliferation, cytotoxicity, antibody production and the release of lymphokines (Strom et al., 1977). We have examined the role of drugs known to involve cyclic nucleotide synthesis or degradation, in modulating the expression of different lymphocyte responses, and have investigated the potential of lithium as a putative blocker of membrane adenylate cyclase, to counter these effects. In this paper we will describe our studies of lithium effects on two aspects of T-cell function, namely the ability to express the receptor for sheep red blood cells (SRBC) and the prolif erative response to a number of mitogens. In the accompanying paper, the effect of lithium on the expression of suppressor cell activity in vitro and in vivo will be discussed.


Adenylate Cyclase Cholera Toxin Cyclic Nucleotide Monovalent Cation Calcium Ionophore A23187 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Chisaro, F.V. and Edgington, T.S., 1974, Human T lymphocytes “E” rosette function, I. A progress modulated by intracellular cyclic AMP, J. Exp. Med. 140:1122.CrossRefGoogle Scholar
  2. Clark, R.B. and Seney, M.N., 1976, Regulation of adenylate cyclase from cultured human cell lines by adenosine, J. Biol. Chem., 251:4239.PubMedGoogle Scholar
  3. Clark, R.B., Gross, R., Su, Y.F., and Perkins, J.P., 1974, Regulation of adenosine 3′:5′-monophosphate content in human astrocytoma cells by adenosine and the adenine nucleotides, J. Biol. Chem., 249:5296.PubMedGoogle Scholar
  4. Galant, S.P. and Remo, R.A., 1975, β-Adrenergic inhibition of human T lymphocyte rosettes, J. Immunol., 114:512.PubMedGoogle Scholar
  5. Gelfand, E.W., Dosch, H-M., Hastings, D., and Shore, A., 1979, Lithium: A modulator of cyclic AMP-dependent events in lymphocytes, Science, 203:365.PubMedCrossRefGoogle Scholar
  6. Grieco, M.H., Siegel, I., and Goel, Z., 1976, Modulation of human T lymphocyte rosette formation by autonomic agonists and cyclic nucleotides, J. Allerg. Clin, Immunol., 58:149.CrossRefGoogle Scholar
  7. Johnson, G.S. and Pastan, I.H., 1971, Change in growth and morphology of fibroblasts by prostaglandins, J. Nat. Cancer Inst., 47:1357.PubMedGoogle Scholar
  8. Limatibul, S., Shore, A., Dosch, H-M., and Gelfand, E.W., 1978, Theophylline modulation of E-rosette formation: An indicator of T-cell maturation, Clin. Exp. Immunol., 33:503.PubMedGoogle Scholar
  9. Marquardt, D.L., Parker, C.W., and Sullivan, T.J., 1978, Potentiation of mast cell mediator release by adenosine, J. Immunol., 120:871.PubMedGoogle Scholar
  10. Meves, H., 1970, The ionic permeability of nerve membranes, in “Permeability and Function of Biological Membranes,” (L. Bolis, A. Katchalski, R.D. Keynes, W.R. Loewenstein, and B.A. Pethica, eds.), Elsevier, Amsterdam.Google Scholar
  11. Peck, W.A., Carpenter, J., and Messinger, K., 1974, Cyclic 3′, 5′-adenosine monophosphate in isolated bone cells. II. Responses to adenosine and parathyroid hormone, Endocrinology, 94:148.PubMedCrossRefGoogle Scholar
  12. Sattin, A. and Rall, T.W., 1970, The effects of adenosine and adenine nucleotides on the cyclic adenosine 3′-5′-phosphate content of guinea pig cerebral cortex slices, Mol. Pharmacol., 6:13.PubMedGoogle Scholar
  13. Schimmer, B.P., 1971, Effects of catecholamines and monovalent cations on adenylate cyclase activity in cultured glial tumor cells, Bioch. Biophys. Acta., 252:567.CrossRefGoogle Scholar
  14. Schwartz, A.L., Stern, R.C., and Polmar, S.H., 1978, Demonstration of an adenosine receptor on human lymphocytes in vitro and its possible role in the adenosine deaminase-deficient form of severe combined immunodeficiency, Clin. Immunol. Immunopath., 9:499.CrossRefGoogle Scholar
  15. Sheppard, J.R., 1971, Restoration of contact-inhibited growth to transformed cells by dibutyryl adenosine 3′:5′-cyclic monophosphate, Proc. Nat. Acad. Sci., 68:1316.PubMedCrossRefGoogle Scholar
  16. Singer, I. and Rotenberg, D., 1973, Mechanisms of lithium action, New Eng. J. Med., 289:254.PubMedCrossRefGoogle Scholar
  17. Smith, J.W., Steiner, A.L., Newberry, W.M., and Parker, C.W., 1971, Cyclic adenosine 3′, 5′-monophosphate in human lymphocytes, Alterations after phytohemagglutinin stimulation, J. Clin. Invest., 50:432.PubMedCrossRefGoogle Scholar
  18. Strom, T.B., Lundin, A.P., and Carpenter, C.B., 1977, The role of cyclic nucleotides in lymphocyte activation and function, Progr. Clin. Immunol., 3:115.Google Scholar
  19. Tolkovsky, A.M. and Levitzki, A., 1978, Coupling of a single adenylate cyclase to two receptors: Adenosine and catecholamine, Biochemistry, 17:3811.PubMedCrossRefGoogle Scholar
  20. Wahl, M. and Kuschinsky, W., 1976, The dilatory action of adenosine on pial arteries of cats and its inhibition by theophylline, Pflueger’s Arch., 362:55.CrossRefGoogle Scholar
  21. Wang, T., Sheppard, J.R., and Foker, J.E., 1978, Rise and fall of cyclic AMP required for onset of lymphocyte DNA synthesis, Science, 201:155.PubMedCrossRefGoogle Scholar
  22. Wolberg, G., Zimmerman, T.P., Hiemstra, K., Winston, M., and Chu, L.C., Adenosine inhibition of lymphocyte-mediated cytolysis: Possible role of cyclic adenosine monophosphate, Science, 187:957.Google Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • E. W. Gelfand
    • 1
  • R. Cheung
    • 1
  • D. Hastings
    • 1
  • H.-M. Dosch
    • 1
  1. 1.Division of Immunology Research InstituteHospital for Sick ChildrenTorontoCanada

Personalised recommendations