Molecular Mechanisms Associated with Cocaine-Induced Modulation of Human T Lymphocytes Proliferation

  • Katsuhiko Matsui
  • Herman Friedman
  • Thomas W. Klein
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 335)


The increasing abuse of cocaine by young adults and the many deaths attributed to cocaine overdose have prompted questions concerning the public health risk of abusing the drug. These deaths result from a combination of drug effects on both the central and sympathetic nervous systems (1). In addition to the lethal toxic effects of cocaine, previous reports demonstrated that cocaine has various influences, both suppression and enhancement, on the immune function of humans and experimental animals (2, 3, 4, 5). However, the mechanisms of immunomodulation in vivo are unclear, because cocaine can act either as a local anesthetic or systemically through the central nervous system.


MgCl Cocaine CaCl Cytosol EGTA 


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  1. 1.
    K. Pearman, Cocaine: A review, J. Laryngol Ontol. 93:1191 (1979).CrossRefGoogle Scholar
  2. 2.
    P. DiFrancesco, F. Pica, C. Croce, C. Favalli, E. Tubaro, and E. Garaci, Effect of acute or daily cocaine administration on cellular immune response and virus infection in mice, Natn.Immun. Cell Growth Regul. 9:397 (1990).Google Scholar
  3. 3.
    D. W. Ou, M. L. Shen, and Y. D. Luo, Effects of cocaine on the immune system of BALB/c mice, Clin. Immunol. Immunopathol. 52:305 (1989).PubMedCrossRefGoogle Scholar
  4. 4.
    O. Bagasra, and L. Forman, Functional analysis of lymphocytes subpopulations in experimental cocaine abuse. I. Dose-dependent activation of lymphocyte subsets, Clin. Exp. Immunol. 77:289 (1989).PubMedGoogle Scholar
  5. 5.
    H. F. Havas, M. Dellaria, G. Schiffman, E. B. Geller, and M. W. Adler, Effect of cocaine on the immune response and host resistance in BALB/c mice, Int. Arch. Allergy Appl.Immunol. 83:377 (1987).PubMedCrossRefGoogle Scholar
  6. 6.
    T. W. Klein, C. A. Newton, and H. Friedman, Suppression of human and mouse lymphocyte proliferation by cocaine, in: “Psychological, Neuropsychiatric and Substance Abuse Aspects of AIDS”, T. P. Bride, ed., pp. 319, Raven Press, New York (1988).Google Scholar
  7. 7.
    J. M. Kanellopoulas, S. Depetris, G. Lecca, and M. J. Crumpton, The mitogenic lectin from Phaseolus vulgaris does not recognize the T3 antigen of human T lymphocytes, Eur. J. Immunol.15.479 (1985).CrossRefGoogle Scholar
  8. 8.
    S. C. Meuer, K. A. Fitzgerald, R. E. Hussey, J. C. Hodgdon, S. F. Schlossman, and E. L. Reinherz, Clonotypic structures involved in antigen-specific human T cell function, J. Exp. Med. 157:705 (1983).PubMedCrossRefGoogle Scholar
  9. 9.
    K. A. Smith, Interleukin-2: Inception, impact and implications, Science 240:1169 (1988).PubMedCrossRefGoogle Scholar
  10. 10.
    G. B. Mills, R. K. Cheung, S. Grinstein, and E. W. Gelfand, Increase in cytosolic free calcium concentration is an intracellular messenger for the production of interleukin-2 but not for expression of the interleukin-2 receptor, J. Immunol 134:1640 (1985).PubMedGoogle Scholar
  11. 11.
    D. K. Blanchard, W. E. Stewart, T. W. Klein, H. Friedman, and J. Y. Djeu, Cytolytic activity of human peripheral blood leukocytes against Legionella pneumophila-infected monocytes: characterization of the effector cell and augmentation by interleukin-2, J. Immunol. 139:551 (1987).PubMedGoogle Scholar
  12. 12.
    J. L. Ceuppens, F. J. Bloemmen, and J. P. Van Wauwe, T cell unresponsiveness to the mitogenic activity of OKT3 antibody results from a deficiency of monocytes Fcr receptors for murine IgG2a and inability to cross-link the T3-Ti complex, J. Immunol. 135:3882 (1985).PubMedGoogle Scholar
  13. 13.
    A. Granelli-Piperno, M. Keane, and R. M. Steinman, Growth factor production and requirements during the proliferative response of human T lymphocytes to anti-CD3 monoclonal antibody, J. Immunol. 142:4138 (1989).PubMedGoogle Scholar
  14. 14.
    M. L. Baroja, and J. L. Ceuppens, More exact quantification of interleukin-2 production by addition of anti-Tac monoclonal antibody to cultures of stimulated lymphocytes, J.Immunologic Methods 98:267 (1987).CrossRefGoogle Scholar
  15. 15.
    R. Y. Tsien, T. Pozzan, and T. J. Rink, Calcium homeotasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator, J. Cell. Biol. 94:325 (1982).PubMedCrossRefGoogle Scholar
  16. 16.
    A. Weiss, J. Imboden, D. Shoback, and J. Stobo, Role of T3 surface molecules in human T-cell activation: T3 dependent activation results in an increase in cytoplasmic free calcium, Proc. Natl. Acad. Sci. USA, 81:4169 (1984).PubMedCrossRefGoogle Scholar
  17. 17.
    G. B. Mills, J. W. W. Lee, R. K. Cheung, and E. W. Gelfand, Characterization of the requirements for human T cell mitogenesis by using suboptimal concentrations of phytohemagglutinin, J. Immunol. 135: 3087 (1985).PubMedGoogle Scholar
  18. 18.
    P. M. Rosoff, and L. C. Cantley, Stimulation of the T3-T cell receptor-associated Ca2+ influx enhances the activity of the Na+ /H+ exchanger in a leukemic human T cell line, J. Biol. Chem. 260:14053 (1985).PubMedGoogle Scholar
  19. 19.
    E. W. Gelfand, R. K. Cheung, and S. Grinstein, Calcium-dependent intracellular acidification dominates the pH response to mitogen in human T cells, J. Immunol. 140:246 (1988).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Katsuhiko Matsui
    • 1
  • Herman Friedman
    • 1
  • Thomas W. Klein
    • 1
  1. 1.Department of Medical Microbiology and ImmunologyUniversity of South Florida College of MedicineTampaUSA

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