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Differential inhibition of primary versus preactivated T cells by pimecrolimus but not by tacrolimus in vitro.

Kalthoff, Frank and Winiski, Anthony and Fichtinger, Petra and Schwendinger, Brigitte and Wang, Shirley and Weishaeupl, Cordula and Stuetz, Anton (2007) Differential inhibition of primary versus preactivated T cells by pimecrolimus but not by tacrolimus in vitro. International Archives of Allergy and Immunology, 142 (3). pp. 255-264. ISSN 1018-2438

Abstract

BACKGROUND: Recent studies in murine models of allergic contact dermatitis have shown that systemic treatment with pimecrolimus in contrast to tacrolimus did not inhibit the sensitization phase, whereas both compounds equivalently suppressed the inflammatory response in sensitized animals. This finding indicated a differential sensitivity of antigen-naïve and primed T cells towards pimecrolimus and tacrolimus. METHODS: T cells obtained from healthy and allergic donors were subjected to primary and secondary stimulation by allogeneic or staphylococcal superantigen-presenting dendritic cells (DC). Human skin-derived, allergen-specific T cell clones from an atopic dermatitis patient were activated by anti-CD3 antibodies or by specific allergen-presenting DC. The inhibition of T cell proliferation and cytokine release by graded doses of calcineurin inhibitors was evaluated. RESULTS: Primary stimulation of T cells was inhibited by pimecrolimus with an approximately 8-fold lower potency as compared with tacrolimus. In contrast, the secondary response of ex vivo expanded T cells activated by allogeneic or staphylococcal superantigen-presenting DC was inhibited by both compounds with equivalent potency. Likewise, both drugs showed very similar potency to inhibit the proliferation and cytokine synthesis from antigen- stimulated T cell clones and the induction of cytokines in Jurkat T cells. CONCLUSION: These data indicate that pimecrolimus has a selectivity for antigen-primed memory T cells not seen with tacrolimus.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); On author or institutional server; Publisher's version/PDF cannot be used
Keywords: Pimecrolimus; Tacrolimus; Primary response; Recall response; T cell
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Date Deposited: 14 Dec 2009 13:50
Last Modified: 31 Jan 2013 01:01
URI: https://oak.novartis.com/id/eprint/996

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