Use this URL to cite or link to this record in EThOS:
Title: Effects of the novel anti-T cell agent FK-506 on the immune system
Author: Woo, J.
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1990
Availability of Full Text:
Access from EThOS:
Results of this study show that the novel immunosuppressant FK-506 is very effective in suppressing lymphocyte activation in various in vitro and in vivo models. This was demonstrated by its strong inhibitory effect on lymphocyte proliferation at concentrations 10 to 100 times lower than that of the conventional immunosuppressant Cyclosporin A. Different sensitivities of lymphocytes to the inhibitory effect of FK-506 were demonstrated. Activation via a CD3-activation pathway was found to be highly sensitive to FK-506, as compared with the less FK-506-sensitive phytohaemagglutinin-induced responses. The reduction of expression of IL-2R caused by FK-506 was, partly a direct effect of FK-506. FK-506 did not influence antigen processing or presentation. Production of IL-1 and induction of HLA-DR expression on antigen presenting cells were shown not to be affected by effective concentrations of FH-506. These results therefore show that FK-506 mainly mediates its effect through CD4+ T lymphocyte activities and thus DTH-type immune functions. This was reflected in vivo by a decrease in numbers of IL-2R+ and OX-40+ (activated CD4+) cells in FK-506-treated immunized animals and then leads to attenuated T- dependent antibody responses, impaired Con A-induced spleen cell proliferation and reduced allogeneic lymphocyte-induced lymph node cell proliferation. Significant, transient suppressor activity was detected in lymph node in FK-506-treated rats. This was further evidenced by a transient increase in splenic CD8+ cells 7 days after drug treatment. These findings thus suggest that the induction of suppressor cells may play an important role in FK-506's immunosuppressive activities. However, other mechanisms such as inhibition of activation of CD4+ T cells, clonal depletion and/or inactivation may also contribute to its immunosuppressive effects in vivo. This can be due to an insufficient supply of lymphokines from CD4+ T cells under treatment with FK-506 to support the proliferation, growth and differentiation of specific clones activated by binding to (allo)-antigens.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available