Inhibition of T-lymphocyte activation by the immunosuppressive drug FK-506

• Published in: Immunology Vol. 67; no. 4; pp. 473 - 477
• Main Authors: KAY, J. E, BENZIE, C. R, GOODIER, M. R, WICK, C. J, DOE, S. E. A
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.08.1989
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; Cells, Cultured; Concanavalin A; Cyclosporins - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Immunosuppressive Agents - pharmacology; Interleukin-2 - pharmacology; Lymphocyte Activation - drug effects; Organs and cells involved in the immune response; Phytohemagglutinins; Pyridines - pharmacology; Recombinant Proteins - pharmacology; RNA, Messenger - analysis; Swine; T-Lymphocytes - drug effects; Tacrolimus; Molecular hybridization; RNA; Activation; Phytohemagglutinin; Concanavalin A; Pig; Northern blotting; Vertebrata; Immunosuppression; Mammalia; T-Lymphocyte; Artiodactyla; Immunosuppressive agent; Inhibition; Ungulata; Nucleic acid
• ISSN: 0019-2805; 1365-2567

Nanamolar concentrations of the immunosuppressive drug FK-506 inhibit the induction of T-lymphocyte proliferation by the lectins concanavalin A (Con A) and phytohaemagglutinin (PHA). Activation by Con A is more sensitive to inhibition than the response to PHA. FK-506 inhibits an early Ca2+-dependent step in the activation process, and its effects are not reversible by the addition of recombinant interleukin-2 (IL-2) or lymphokine-rich culture supernatant. While the effects of suboptimal concentrations of FK-506 and cyclosporin A (CsA) are additive, FK-506 does not enhance the effects of optimal concentrations of CsA. Both drugs also have similar effects on the expression of specific mRNA in Con A-activated lymphocytes. A brief preincubation of unstimulated cells with FK-506 irreversibly inhibits their subsequent responsiveness to Con A. The mechanism of action of FK-506 thus resembles that of CsA, except that it is effective at two to three orders of magnitude lower concentrations and its effects are much less readily reversible.