LYMPHOTACTIN - A KEY REGULATOR OF LYMPHOCYTE TRAFFICKING DURING ACUTEGRAFT-REJECTION

The attraction of leucocytes to allografts is essential for rejection. The process is controlled by chemokines. In order to clarify the role of lymphotactin (a cytokine that represents a novel branch of the che mokine superfamily) in regulating leucocyte trafficking during graft r ejection, we used rat renal transplantation models to examine its gene expression and the distribution of lymphotactin-expressing cells in r enal grafts. Lymphotactin mRNA was upregulated strongly in acutely rej ecting renal allografts. The mRNA was undetectable in isografts, chron ically rejecting renal allografts or normal kidney. Once lymphotactin was expressed, large numbers of infiltrating lymphocytes were seen. Mo reover extended studies demonstrated that in cultured rat spleen cells the expression of lymphotactin mRNA was markedly induced by phytohaem agglutinin (PHA) or phorbol myristate acetate (PMA), and such inductio n was inhibited by the immunosuppressive drugs FK506 and cyclosporin. Collectively, these observations provide new evidence demonstrating th at lymphotactin is a key regulator of lymphocyte motility and adhesive ness during acute allograft rejection. FK506 and cyclosporin inhibitio n of lymphotactin expression is likely to represent an important molec ular mechanism of the action of the drugs.