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(Journal of Leukocyte Biology. 2002;71:289-294.)
© 2002 by Society for Leukocyte Biology

Cyclosporin A inhibition of macrophage colony-stimulating factor (M-CSF) production by activated human T lymphocytes

Stéphanie Frétier^*, Arnaud Besse, Adriana Delwail^*, Martine Garcia^*, Franck Morel^*, Valérie Leprivey-Lorgeot, John Wijdenes, Vincent Praloran and Jean-Claude Lecron^*

^* Laboratoire Cytokines, FRE 2224, IFR FR 59, IBMIG, Université de Poitiers, Cedex, France;
Laboratoire Universitaire d’Hématologie, EA 482, Université de Bordeaux 2, France;
Laboratoire de Physiologie, Faculté de Médecine, Université de Limoges, Cedex, France; and
Laboratoire Diaclone, BP 1985, Besançon, France

Correspondence: J. C. Lecron, Laboratoire Cytokines, FRE 2224, IFR FR 59, IBMIG, Université de Poitiers, 40, avenue du Recteur Pineau, 86022 Poitiers, Cedex, France. E-mail: Jean-Claude.Lecron{at}univ-poitiers.fr

M-CSF is a pleiotropic cytokine involved in the survival, proliferation, and differentiation of cells of the monocyte/macrophage lineage. M-CSF is produced by numerous cells including CD3-activated T cells. M-CSF serum levels are increased during acute graft rejection. We tested the in vitro production of M-CSF, GM-CSF, IL-2, and IL-4 by T-cell clones costimulated by CD3 and accessory activation pathways and the effects of cyclosporin A and methylprednisolone. The nine clones studied and CD4+ cells purified from peripheral blood mononuclear cells (PBMC) spontaneously produced low levels of M-CSF, which PMA and CD3 mAb strongly enhanced. In contrast to IL-2, CD28 mAb did not further enhance this production. CsA inhibited M-CSF production by clones and purified CD4 T cells. Addition of IL-2, anti IL-2, or anti CD25 mAb to the cultures demonstrated that CsA down-regulated M-CSF synthesis by activated T cells through its inhibition of IL-2 synthesis. These results could help to better understand the complex mechanisms of acute graft rejection and immunosuppression.

Key Words: immunosuppression • graft-versus-host • TNF- • PMA

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