Abstract
Cyclosporin A inhibited at equal concentration both pokeweed mitogen and Staphylococcus aureus Cowan I-induced in vitro proliferative activity of blood leucocytes, intracellular immunoglobulin synthesis and release of immunoglobulin to the culture medium. When the interacting lymphoid cell subpopulations, T cells, B cells, T gamma and T micro cells were fractionated apart and separately stimulated with these mitogens, cyclosporin A inhibited again at equal concentrations pokeweed mitogen-induced proliferation of blood T gamma, T micro and B cells and Staphylococcus-induced proliferation of B cells. The 50% inhibitory concentration varied in separate experiments between 10(-2)-10(-1) microgram/ml. Although cyclosporin A efficiently suppressed the blastogenic response, a 100- to 1,000-fold concentration of the drug was required to damage resting lymphocytes in culture. After the blastogenic phase, pokeweed mitogen-stimulated blood leucocytes were again resistant to cyclosporin A: intracellular Ig synthesis and release of Ig to the culture medium proceeded independently of the presence of the drug. As the phagocytic activity of mononuclear phagocytes was not affected by prior culture in cyclosporin A-containing medium, we conclude that in man cyclosporin A suppression both T and B lymphocyte blastogenesis, and that the suppression is due to a direct effect on the blast cell rather than mediated via a third-party accessory cell.
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Selected References
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- Borel J. F., Feurer C., Gubler H. U., Stähelin H. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions. 1976 Jul;6(4):468–475. doi: 10.1007/BF01973261. [DOI] [PubMed] [Google Scholar]
- Calne R. Y., White D. J., Rolles K., Smith D. P., Herbertson B. M. Prolonged survival of pig orthotopic heart grafts treated with cyclosporin A. Lancet. 1978 Jun 3;1(8075):1183–1185. doi: 10.1016/s0140-6736(78)90971-6. [DOI] [PubMed] [Google Scholar]
- Cunningham A. J. A method of increased sensitivity for detecting single antibody-forming cells. Nature. 1965 Sep 4;207(5001):1106–1107. doi: 10.1038/2071106a0. [DOI] [PubMed] [Google Scholar]
- Forsgren A., Svedjelund A., Wigzell H. Lymphocyte stimulation by protein A of Staphylococcus aureus. Eur J Immunol. 1976 Mar;6(3):207–213. doi: 10.1002/eji.1830060312. [DOI] [PubMed] [Google Scholar]
- Gehrz R. C., Knorr S. O. Characterization of the role of mononuclear cell subpopulations in the in vitro lymphocyte proliferation assay. Clin Exp Immunol. 1979 Sep;37(3):551–557. [PMC free article] [PubMed] [Google Scholar]
- Gordon M. Y., Singer J. W. Selective effects of cyclosporin A on colony-forming lymphoid and myeloid cells in man. Nature. 1979 May 31;279(5712):433–434. doi: 10.1038/279433a0. [DOI] [PubMed] [Google Scholar]
- Green C. J., Allison A. C. Extensive prolongation of rabbit kidney allograft survival after short-term cyclosporin-A treatment. Lancet. 1978 Jun 3;1(8075):1182–1183. doi: 10.1016/s0140-6736(78)90970-4. [DOI] [PubMed] [Google Scholar]
- Homan W. P., Fabre J. W., Morris P. J. Nature of the unresponsiveness induced by cyclosporin A in rats bearing renal allografts. Transplantation. 1979 Nov;28(5):439–441. doi: 10.1097/00007890-197911000-00023. [DOI] [PubMed] [Google Scholar]
- Janossy G., Greaves M. Functional analysis of murine and human B lymphocyte subsets. Transplant Rev. 1975;24:177–236. doi: 10.1111/j.1600-065x.1975.tb00169.x. [DOI] [PubMed] [Google Scholar]
- Moretta L., Mingari M. C., Moretta A., Cooper M. D. Human T lymphocyte subpopulations: studies of the mechanism by which T cells bearing Fc receptors for IgG suppress T-dependent B cell differentiation induced by pokeweed mitogen. J Immunol. 1979 Mar;122(3):984–990. [PubMed] [Google Scholar]
- Waldron J. A., Jr, Horn R. G., Rosenthal A. S. Antigen-induced proliferation of guinea pig lymphocytes in vitro: obligatory role of macrophages in the recognition of antigen by immune T-lymphocytes. J Immunol. 1973 Jul;111(1):58–64. [PubMed] [Google Scholar]
- White D. J., Plumb A. M., Pawelec G., Brons G. Cyclosporin A: an immunosuppressive agent preferentially active against proliferating T cells. Transplantation. 1979 Jan;27(1):55–58. [PubMed] [Google Scholar]