Cell-surface trafficking and release of flt3 ligand from T lymphocytes is induced by common cytokine receptor γ-chain signaling and inhibited by cyclosporin A

Elena Chklovskaia, Catherine Nissen, Lukas Landmann, Christoph Rahner, Otmar Pfister, Aleksandra Wodnar-Filipowicz

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The flt3 ligand (FL) is a growth and differentiation factor for primitive hematopoietic precursors, dendritic cells, and natural killer cells. Human T lymphocytes express FL constitutively, but the cytokine is retained intracellularly within the Golgi complex. FL is mobilized from the cytoplasmic stores and its serum levels are massively increased during the period of bone marrow aplasia after stem cell transplantation (SCT). Signals that trigger the release of FL by T cells remain unknown. This study shows that interleukin (IL)-2, IL-4, IL-7, and IL-15, acting through a common receptor γ, chain (γc), but not cytokines interacting with other receptor families, are efficient inducers of cell surface expression of membrane-bound FL (mFL) and secretion of soluble FL (sFL) by human peripheral blood T lymphocytes. The γc-mediated signaling up-regulated FL in a T-cell receptor-independent manner. IL-2 and IL-7 stimulated both FL messenger RNA (mRNA) expression and translocation of FL protein to the cell surface. Cyclosporin A (CsA) inhibited γc-mediated trafficking of FL at the level of transition from the Golgi to the trans-Golgi network. Accordingly, serum levels of sFL and expression of mFL by T cells of CsA-treated recipients of stem cell allografts were reduced approximately 2-fold (P < .01) compared to patients receiving autologous grafts. The conclusion is that FL expression is controlled by γc receptor signaling and that CsA interferes with FL release by T cells. The link between γc-dependent T-cell activation and FL expression might be important for T-cell effector functions in graft acceptance and antitumor immunity after SCT.

Original languageEnglish
Pages (from-to)1027-1034
Number of pages8
JournalBlood
Volume97
Issue number4
Publication statusPublished - 15 Feb 2001
Externally publishedYes

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