Probing Immune Responses: The Role of Intracellular Glutathione

  • Mario Roederer
  • Leonard A. Herzenberg
Part of the Developments in Oncology book series (DION, volume 77)


The power of flow cytometry is evidenced by its ability to measure a variety of parameters on a cell-by-cell basis. The utility of flow cytometric measurements of these parameters becomes evident when it is understood that, for a population of cells, the distribution of these parameters can be determined. Thus, the heterogeneity within cell populations can be determined. This obviates the need for the assumption that an average value obtained for a population of cells (as obtained using a bulk analysis) is representative for each cell within that population.


Peripheral Blood Mononuclear Cell Intracellular Glutathione Buthionine Sulfoximine Single Positive Intracellular Glutathione Level 
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. 1.
    Roederer M, Ela SW, Staal FJT, et al: N-acetylcysteine: A new approach to anti-HIV therapy. AIDS Res. Human Retr. 8:209–217, 1992.CrossRefGoogle Scholar
  2. 2.
    Roederer M, Staal FJT, Osada H, et al: CD4 and CD8 T cells with high intracellular glutathione levels are selectively lost as the HIV infection progresses. Intl. Immunol. 3:933–937, 1991.CrossRefGoogle Scholar
  3. 3.
    Eck H-P, Gmunder H, Hartmann M, et al: Low Concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1-infected patients. Biol. Chem. Hoppe-Seyler 370:101–108, 1989.PubMedCrossRefGoogle Scholar
  4. 4.
    Buhl R, Holroyd KJ, Mastrangeli A, et al: Systemic glutathione deficiency in asymptomatic HIV-seropositive individuals. Lancet ii:1294–1298, 1989.CrossRefGoogle Scholar
  5. 5.
    Staal FJT, Roederer M, Israelski DM, et al: Intracellular glutathione levels in T cell subsets decrease in HIV infected individuals. AIDS Res. Human Retr. 8:311–318, 1992.Google Scholar
  6. 6.
    Fischman CH, Udey MC, Kurtz M, Wedner HJ: Inhibition of lectin-induced lymphocyte activation by 2-cyclohexene-l-one: Decreased intracellular gluta-thione inhibits an early event in the activation sequence. J. Immunol. 127:2257–2262, 1981.PubMedGoogle Scholar
  7. 7.
    Fidelus RK, Tsan M-F: Enhancement of intracellular glutathione promotes lymphocyte activation by mitogen. Cell. Immunol. 97:155–163, 1986.PubMedCrossRefGoogle Scholar
  8. 8.
    Fidelus RK, Ginouves P, Lawrence D, Tsan M-F: Modulation of intracellular glutathione concentrations alters lymphocyte activation and proliferation. Exp. Cell Res. 170:269–275, 1987.PubMedCrossRefGoogle Scholar
  9. 9.
    Fidelus RK: The generation of oxygen radicals: A positive signal for lymphocyte activation. Cell. Immunol. 113:175–182, 1988.PubMedCrossRefGoogle Scholar
  10. 10.
    Suthanthiran M, Anderson ME, Sharma VK, Meister A: Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. Proc. Natl. Acad. Sci. USA 87:3343–3347, 1990.PubMedCrossRefGoogle Scholar
  11. 11.
    Messina JP, Lawrence DA: Cell cycle progression of glutathione-depleted human peripheral blood mononuclear cells is inhibited at S phase. J. Immunol. 143:1974–1981, 1989.PubMedGoogle Scholar
  12. 12.
    Ballard DW, Bohnlein E, Lowenthal JW, et al: HTLV-I Tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene. Science 241:1652–1655, 1988.PubMedCrossRefGoogle Scholar
  13. 13.
    Lowenthal JW, Ballard DW, Bohnlein E, Greene WC: Tumor necrosis factor alpha induces proteins that bind specifically to kappaB-like enhancer elements and regulate interleukin 2 receptor alpha-chain gene expression in primary human T lymphocytes. Proc. Natl. Acad. Sci. USA 86:2331–2335, 1989.PubMedCrossRefGoogle Scholar
  14. 14.
    Shibuya H, Yoneyama M, Taniguchi T: Involvement of a common transcription factor in the regulated expression of IL-2 and IL-2 receptor genes. Intl. Immunol. 1:43–49, 1989.CrossRefGoogle Scholar
  15. 15.
    Gmunder H, Roth S, Eck H-P, et al: Interleukin-2 messenger RNA expression, lymphokine production and DNA synthesis in glutathione-depleted T-cells. Cell. Immunol. 130:520–528, 1990.PubMedCrossRefGoogle Scholar
  16. 16.
    Gmunder H, Eck H-P, Benninghoff B, et al: Macrophages regulate intracellular glutathione levels of lymphocytes. Evidence for an immunoregulatory role of cysteine. Cell. Immunol. 129:32–46, 1990.PubMedCrossRefGoogle Scholar
  17. 17.
    Hamilos DL, Wedner HJ: The role of glutathione in lymphocyte activation. I. Comparison of inhibitory effects of buthionine sulfoximine and 2-cyclohexene-1-one by nuclear size transformation. J. Immunol. 135:2740–2747, 1985.Google Scholar
  18. 18.
    Hamilos DL, Zelarney P, Mascali JJ: Lymphocyte proliferation in glutathione-depleted lymphocytes: Direct relationship between glutathione availability and the proliferative response. Immunopharmacology 18:223–235, 1989.PubMedCrossRefGoogle Scholar
  19. 19.
    Droge W, Pottmeyer-Gerber C, Schmidt H, Nick S: Glutathione augments the activation of cytotoxic T lymphocytes in vivo. Immunobiol. 172:151–156, 1986.Google Scholar
  20. 20.
    Roederer M, Staal FJT, Raju PA, et al: Cytokine-stimulated HIV replication is inhibited by N-acetylcysteine. Proc. Natl. Acad. Sci. USA 87:4884–4888, 1990.PubMedCrossRefGoogle Scholar
  21. 21.
    Roederer M, Raju PA, Staal FJT, et al: N-Acetylcysteine inhibits latent HIV expression in chronically-infected cells. AIDS Res. Human Retr.7:491–495, 1991.Google Scholar
  22. 22.
    Kalebic T, Kinter A, Poli G, et al: Suppression of HIV expression in chronically infected monocytic cells by glutathione, glutathione ester, and N-acetylcysteine. Proc. Natl. Acad. Sci. USA 88:986–990, 1991.PubMedCrossRefGoogle Scholar
  23. 23.
    Mihm S, Ennen J, Pessara U, et al: Inhibition of HIV-1 replication and NF-kappaB activity by cysteine and cysteine derivatives. AIDS 5:497–503, 1991.PubMedCrossRefGoogle Scholar
  24. 24.
    Staal FJT, Roederer M, Herzenberg LA, Herzenberg LA: Intracellular thiols regulate activation of nuclear factor kB and transcription of human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 87:9943–9947, 1990.PubMedCrossRefGoogle Scholar
  25. 25.
    Schreck R, Rieber P, Baeuerle PA: Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappaB transcription factor and HIV-1. EMBO J. 10:2247–2258, 1991.PubMedGoogle Scholar
  26. 26.
    Roederer M, Fiering SN, Herzenberg LA: FACS-Gal: Flow cytometric analysis and sorting of cells expressing reporter gene constructs. Methods: A Companion to Methods in Enzymology 2:248–260, 1991.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Mario Roederer
  • Leonard A. Herzenberg

There are no affiliations available

Personalised recommendations