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. 1989 Aug;67(4):473–477.

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

J E Kay 1, C R Benzie 1, M R Goodier 1, C J Wick 1, S E Doe 1
PMCID: PMC1385316  PMID: 2475433

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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