Abstract
One contributing factor to the loss of T cells in AIDS may be the impaired ability of T cell precursors to expand, as reflected in a decreased ability of patient cells to form T cell colonies in agar. We and others have noted such a defect in people with AIDS and ARC, and have found that suppressor cells and suppressive plasma contribute to decreased T-CFC formation. We report here that the reducing agents 2-mercaptoethanol (2-ME) and n-acetyl cysteine (NAC) can enhance colony formation in vitro. In part, 2-ME can reverse the defect in T cell colony-forming cells (T-CFC) formation by overcoming the effect of suppressor cells. In a group of 46 AIDS patients, T-CFC formation was initially 42 +/- 8% (mean +/- s.e.) that of control levels. 2-ME caused an increase of 401 +/- 76% in T-CFC formation which was significantly greater than the increase in control T-CFC formation; it also significantly enhanced T-CFC formation by cells from ARC patients. Suppressor cell activity from ten AIDS patients decreased from 58 +/- 21% to 12 +/- 10% when 2-ME was added. Similar data were obtained from 14 ARC patients. NAC, a related antioxidant with low toxicity, also enhanced T-CFC in cells of AIDS and ARC patients. Vitamin C generally did not increase T-CFC formation. The data suggest that certain antioxidants such as 2-ME and NAC may be useful in treatment protocols to enhance T cell numbers in patients with AIDS or ARC.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Axelsson J. A., Källén B., Nilsson O., Tropé C. Effect of 2-mercaptoethanol on the mixed leukocyte reaction in man. Probable effect on blastogenic factor stabilization. Acta Pathol Microbiol Scand C. 1976 Oct;84C(5):390–396. doi: 10.1111/j.1699-0463.1976.tb00046.x. [DOI] [PubMed] [Google Scholar]
- Chaplin D. D., Wedner J. H. Inhibition of lectin-induced lymphocyte activation by diamide and other sulfhydryl reagents. Cell Immunol. 1978 Mar 15;36(2):303–311. doi: 10.1016/0008-8749(78)90274-5. [DOI] [PubMed] [Google Scholar]
- Claësson M. H., Flad H. D., Opitz H. G. B and T lymphocyte colony formation in agar: 2-mercaptoethanol-activated albumin can substitute for 2-mercaptoethanol. Cell Immunol. 1979 Sep 1;46(2):398–404. doi: 10.1016/0008-8749(79)90426-x. [DOI] [PubMed] [Google Scholar]
- De Flora S., Rossi G. A., De Flora A. Metabolic, desmutagenic and anticarcinogenic effects of N-acetylcysteine. Respiration. 1986;50 (Suppl 1):43–49. doi: 10.1159/000195087. [DOI] [PubMed] [Google Scholar]
- Fanger M. W., Hart D. A., Wells J. V., Nisonoff A. Enhancement by reducing agents of the transformation of human and rabbit peripheral lymphocytes. J Immunol. 1970 Oct;105(4):1043–1045. [PubMed] [Google Scholar]
- Fauci A. S., Macher A. M., Longo D. L., Lane H. C., Rook A. H., Masur H., Gelmann E. P. NIH conference. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations. Ann Intern Med. 1984 Jan;100(1):92–106. doi: 10.7326/0003-4819-100-1-92. [DOI] [PubMed] [Google Scholar]
- Forsdyke D. R., David C. M. Comparison of enhancement by heated serum and 2-mercaptoethanol of lymphocyte transformation induced by high concentrations of concanavalin A. Cell Immunol. 1978 Mar 1;36(1):86–96. doi: 10.1016/0008-8749(78)90253-8. [DOI] [PubMed] [Google Scholar]
- Heber-Katz E., Click R. E. Immune responses in vitro. V. Role of mercaptoethanol in the mixed-leukocyte reaction. Cell Immunol. 1972 Nov;5(3):410–418. doi: 10.1016/0008-8749(72)90067-6. [DOI] [PubMed] [Google Scholar]
- Hoffeld J. T., Oppenheim J. J. Enhancement of the primary antibody response by 2-mercaptoethanol is mediated by its action on glutathione in the serum. Eur J Immunol. 1980 May;10(5):391–395. doi: 10.1002/eji.1830100514. [DOI] [PubMed] [Google Scholar]
- Laurence J., Gottlieb A. B., Kunkel H. G. Soluble suppressor factors in patients with acquired immune deficiency syndrome and its prodrome. Elaboration in vitro by T lymphocyte-adherent cell interactions. J Clin Invest. 1983 Dec;72(6):2072–2081. doi: 10.1172/JCI111172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laurence J., Mayer L. Immunoregulatory lymphokines of T hybridomas from AIDS patients: constitutive and inducible suppressor factors. Science. 1984 Jul 6;225(4657):66–69. doi: 10.1126/science.6328662. [DOI] [PubMed] [Google Scholar]
- Levy E. M., Beldekas J. C., Mayer K. H., Black P. H. Defective T-cell differentiation in acquired immune deficiency syndrome (AIDS). J Clin Immunol. 1986 Mar;6(2):152–160. doi: 10.1007/BF00918748. [DOI] [PubMed] [Google Scholar]
- Metcalf D. Role of mercaptoethanol and endotoxin in stimulating B lymphocyte colony formation in vitro. J Immunol. 1976 Mar;116(3):635–638. [PubMed] [Google Scholar]
- Moldéus P., Cotgreave I. A., Berggren M. Lung protection by a thiol-containing antioxidant: N-acetylcysteine. Respiration. 1986;50 (Suppl 1):31–42. doi: 10.1159/000195086. [DOI] [PubMed] [Google Scholar]
- Winkelstein A., Kingsley L. A., Klein R. S., Lyter D. W., Evans T. L., Rinaldo C. R., Jr, Weaver L. D., Machen L. L., Schadle R. C. Defective T-cell colony formation and IL-2 receptor expression at all stages of HIV infection. Clin Exp Immunol. 1988 Mar;71(3):417–422. [PMC free article] [PubMed] [Google Scholar]
- Winkelstein A., Klein R. S., Evans T. L., Dixon B. W., Holder W. L., Weaver L. D. Defective in vitro T cell colony formation in the acquired immunodeficiency syndrome. J Immunol. 1985 Jan;134(1):151–156. [PubMed] [Google Scholar]
- Ziment I. Acetylcysteine: a drug with an interesting past and a fascinating future. Respiration. 1986;50 (Suppl 1):26–30. doi: 10.1159/000195085. [DOI] [PubMed] [Google Scholar]