In vitro and in vivo action of cyclosporin A on the induction of human interleukin-2 receptor alpha and beta chains.
To compare in vitro and in vivo cyclosporin A (CyA) effects on early events involved in human T cell activation, lymphocytes obtained from healthy donors and from diabetic patients undergoing CyA therapy were studied for their interleukin 2 (IL-2) responsiveness, surface IL-2 receptor (IL-2R) expression and IL-2R mRNA accumulation, following stimulation with mitogen or anti-CD3 monoclonal antibody. T cells recovered from eight in vivo CyA-treated patients and stimulated in vitro for 4 h with mitogen or anti-CD3 (in the absence of CyA) showed significant (50-60%) inhibition of Tac mRNA accumulation, as assessed and quantified by scanning densitometry. Conversely, these cells showed no modification in their expression of membrane alpha (p55, Tac) or beta (p70) chains of IL-2R in binding experiments performed with both iodinated anti-Tac and IL-2 following 18 h stimulation with either mitogen or anti-CD3. Normal lymphocytes treated in vitro with CyA showed significant inhibition of alpha chain IL-2R expression both at the mRNA and the membrane level. At variance, expression of the IL-2R beta chain was unaffected; a significant number of high-affinity IL-2 binding sites was still detectable after in vitro CyA treatment. These results suggest that: (1) a residual immunosuppressive effect of CyA on T cell activation may be evidenced in in vivo treated cells by measuring very early events triggered following short-term stimulation; (2) CyA activity on T cell activation seems similar in vivo and in vitro; and (3) the described approach would be potentially useful to monitor the individual in vivo immunosuppressive capacity of CyA.
Caillat-Zucman
S
S
INSERM U 25, Hôpital Necker, Paris, France.
Chatenoud
L
L
Bach
J F
JF
D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013601:T-Lymphocytes / Q000187:drug effects*
D003524:Cyclosporins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2