Abstract
We examined the effect of new immunosuppressive agent, FK506, on the human B cell function, in comparison with that of cyclosporin A (CyA) and tried to define the discrete activation step(s) which is selectively affected by FK506 and CyA. We used polyclonal B cell activators, Staphylococcus aureus Cowan I (SAC) and pokeweed mitogen (PWM). We found that (i) the initial B cell activation process by PWM, which is on the basis of T cell-dependent manner, is susceptible to the inhibitory effects of FK506 and CyA, while initial B cell activation on the basis of T cell-independent manner by SAC is resistant to these drugs; (ii) they also inhibit helper factor production by T cells; (iii) once they are activated, the B cells become resistant to inhibition by the drugs; and (iv) on an equimolar basis, FK506 exhibits 100-fold greater inhibitory activity than does CyA. Thus FK506 mainly interferes with interactions between T cells and other cells which are essential for B cell activation process, resulting in inhibition of B cell function.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bickel M., Tsuda H., Amstad P., Evequoz V., Mergenhagen S. E., Wahl S. M., Pluznik D. H. Differential regulation of colony-stimulating factors and interleukin 2 production by cyclosporin A. Proc Natl Acad Sci U S A. 1987 May;84(10):3274–3277. doi: 10.1073/pnas.84.10.3274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Borel J. F., Feurer C., Magnée C., Stähelin H. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977 Jun;32(6):1017–1025. [PMC free article] [PubMed] [Google Scholar]
- Collier D. S., Thiru S., Calne R. Kidney transplantation in the dog receiving FK-506. Transplant Proc. 1987 Oct;19(5 Suppl 6):62–62. [PubMed] [Google Scholar]
- Dongworth D. W., Klaus G. G. Effects of cyclosporin A on the immune system of the mouse. I. Evidence for a direct selective effect of cyclosporin A on B cells responding to anti-immunoglobulin antibodies. Eur J Immunol. 1982 Dec;12(12):1018–1022. doi: 10.1002/eji.1830121207. [DOI] [PubMed] [Google Scholar]
- Kino T., Hatanaka H., Hashimoto M., Nishiyama M., Goto T., Okuhara M., Kohsaka M., Aoki H., Imanaka H. FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo) 1987 Sep;40(9):1249–1255. doi: 10.7164/antibiotics.40.1249. [DOI] [PubMed] [Google Scholar]
- Kino T., Hatanaka H., Miyata S., Inamura N., Nishiyama M., Yajima T., Goto T., Okuhara M., Kohsaka M., Aoki H. FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo) 1987 Sep;40(9):1256–1265. doi: 10.7164/antibiotics.40.1256. [DOI] [PubMed] [Google Scholar]
- Kishimoto T., Yoshizaki K., Kimoto M., Okada M., Kuritani T., Kikutani H., Shimizu K., Nakagawa T., Nakagawa N., Miki Y. B cell growth and differentiation factors and mechanism of B cell activation. Immunol Rev. 1984 Apr;78:97–118. doi: 10.1111/j.1600-065x.1984.tb00478.x. [DOI] [PubMed] [Google Scholar]
- Lim S. M., Thiru S., White D. J. Heterotopic heart transplantation in the rat receiving FK-506. Transplant Proc. 1987 Oct;19(5 Suppl 6):68–70. [PubMed] [Google Scholar]
- Muraguchi A., Butler J. L., Kehrl J. H., Falkoff R. J., Fauci A. S. Selective suppression of an early step in human B cell activation by cyclosporin A. J Exp Med. 1983 Sep 1;158(3):690–702. doi: 10.1084/jem.158.3.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ochiai T., Nagata M., Nakajima K., Sakamoto K., Asano T., Isono K. Prolongation of canine renal allograft survival by treatment with FK-506. Transplant Proc. 1987 Oct;19(5 Suppl 6):53–56. [PubMed] [Google Scholar]
- Paavonen T., Häyry P. Effect of cyclosporin A on T-dependent and T-independent immunoglobulin synthesis in vitro. Nature. 1980 Oct 9;287(5782):542–544. doi: 10.1038/287542a0. [DOI] [PubMed] [Google Scholar]
- Sawada S., Suzuki G., Kawase Y., Takaku F. Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation. J Immunol. 1987 Sep 15;139(6):1797–1803. [PubMed] [Google Scholar]
- Shevach E. M. The effects of cyclosporin A on the immune system. Annu Rev Immunol. 1985;3:397–423. doi: 10.1146/annurev.iy.03.040185.002145. [DOI] [PubMed] [Google Scholar]
- Snyder D. S., Wright C. L., Ting C. Inhibition of human monocyte antigen presentation, but not HLA-DR expression, by cyclosporine. Transplantation. 1987 Sep;44(3):407–411. doi: 10.1097/00007890-198709000-00016. [DOI] [PubMed] [Google Scholar]
- Suzuki N., Sakane T. Mechanism of T cell-derived helper factor production upon stimulation with pokeweed mitogen in humans. Clin Exp Immunol. 1988 Feb;71(2):343–349. [PMC free article] [PubMed] [Google Scholar]
- Suzuki N., Sakane T., Ueda Y., Murakawa Y., Tsunematsu T. Implications for the role of cognate interactions in in vitro human B cell activation by Staphylococcus aureus Cowan I and pokeweed mitogen. J Clin Invest. 1986 Jan;77(1):294–300. doi: 10.1172/JCI112290. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suzuki N., Ueda Y., Sakane T. Differential mechanism for differentiation into immunoglobulin-secreting cells in human resting B lymphocyte subsets isolated on the basis of cell density. J Clin Invest. 1988 Jan;81(1):261–269. doi: 10.1172/JCI113304. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshimura N., Matsui S., Hamashima T., Oka T. Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. I. Inhibition of expression of alloantigen-activated suppressor cells, as well as induction of alloreactivity. Transplantation. 1989 Feb;47(2):351–356. doi: 10.1097/00007890-198902000-00034. [DOI] [PubMed] [Google Scholar]
- Zeevi A., Duquesnoy R., Eiras G., Rabinowich H., Todo S., Makowka L., Starzl T. E. Immunosuppressive effect of FK-506 on in vitro lymphocyte alloactivation: synergism with cyclosporine A. Transplant Proc. 1987 Oct;19(5 Suppl 6):40–44. [PMC free article] [PubMed] [Google Scholar]