TY - JOUR
T1 - Inhibition of antigen-specific activation of an L3T4+ T cell line by cyclosporine with maintenance of macrophage-mediated antigen presentation
AU - Lu, C. Y.
AU - Lemay, P. A.
AU - Lombardi, M. J.
PY - 1988/1
Y1 - 1988/1
N2 - Cyclosporine has clearly been shown to directly inhibit T lymphocyte activation by monoclonal antibodies or mitogens where nominal antigen and accessory cells are not present. However, when T lymphocytes are stimulated by antigen, as occurs in allograft rejection, T lymphocytes and accessory cells must interact with one another. Under the latter circumstances, the issue of whether cyclosporine acts on T lymphocyte, accessory cell, or both is not resolved. This issue is addressed in this study. To assess the effect of cyclosporine on T cell activation, macrophages were incubated with heat-killed Listeria and then fixed in paraformaldehyde. These fixed macrophages retained their ability to present antigen to T cells but were not affected by subsequent treatment with cyclosporine. When cyclosporine and a L3T4* T lymphocyte line were added simultaneously to fixed, antigen-pulsed macrophages, the drug inhibited antigen-specific T cell activation with a half maximal inhibitory concentration of 10 ng/ml. To our knowledge, this is the first evidence that low doses of cyclosporine inhibit antigen-specific T cell activation where the drug's effects on antigen-presenting cells have been excluded. To assess the effects of cyclosporine on macrophage-mediated antigen-presentation, macrophages were exposed simultaneously to cyclosporine and antigen, and then fixed. Antigen-presentation was not inhibited unless extremely large doses (9000 ng/ml) of cyclosporine were used. In our experimental system, any new inhibitory activity acquired by live cyclosporine-treated macrophages could be explained by residual drug. Finally, cyclosporine did not inhibit the induction of macrophage la expression nor antigen-presenting function after stimulation in vitro with lymphokine.
AB - Cyclosporine has clearly been shown to directly inhibit T lymphocyte activation by monoclonal antibodies or mitogens where nominal antigen and accessory cells are not present. However, when T lymphocytes are stimulated by antigen, as occurs in allograft rejection, T lymphocytes and accessory cells must interact with one another. Under the latter circumstances, the issue of whether cyclosporine acts on T lymphocyte, accessory cell, or both is not resolved. This issue is addressed in this study. To assess the effect of cyclosporine on T cell activation, macrophages were incubated with heat-killed Listeria and then fixed in paraformaldehyde. These fixed macrophages retained their ability to present antigen to T cells but were not affected by subsequent treatment with cyclosporine. When cyclosporine and a L3T4* T lymphocyte line were added simultaneously to fixed, antigen-pulsed macrophages, the drug inhibited antigen-specific T cell activation with a half maximal inhibitory concentration of 10 ng/ml. To our knowledge, this is the first evidence that low doses of cyclosporine inhibit antigen-specific T cell activation where the drug's effects on antigen-presenting cells have been excluded. To assess the effects of cyclosporine on macrophage-mediated antigen-presentation, macrophages were exposed simultaneously to cyclosporine and antigen, and then fixed. Antigen-presentation was not inhibited unless extremely large doses (9000 ng/ml) of cyclosporine were used. In our experimental system, any new inhibitory activity acquired by live cyclosporine-treated macrophages could be explained by residual drug. Finally, cyclosporine did not inhibit the induction of macrophage la expression nor antigen-presenting function after stimulation in vitro with lymphokine.
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U2 - 10.1097/00007890-198801000-00039
DO - 10.1097/00007890-198801000-00039
M3 - Article
C2 - 3257307
AN - SCOPUS:0023864797
SN - 0041-1337
VL - 45
SP - 187
EP - 194
JO - Transplantation
JF - Transplantation
IS - 1
ER -