Cyclosporin A inhibition of macrophage colony-stimulating factor (M-CSF) production by activated human T lymphocytes.
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.
Frétier
Stéphanie
S
Laboratoire Cytokines, FRE 2224, IFR FR 59, IBMIG, Université de Poitiers, Cedex, France.
Besse
Arnaud
A
Delwail
Adriana
A
Garcia
Martine
M
Morel
Franck
F
Leprivey-Lorgeot
Valérie
V
Wijdenes
John
J
Praloran
Vincent
V
Lecron
Jean-Claude
JC
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology*; D003864:Depression, Chemical; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D008775:Methylprednisolone / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016572:Cyclosporine; D008775:Methylprednisolone