THE EFFECTS OF MONOCYTES ON THE TRANSENDOTHELIAL MIGRATION OF T-LYMPHOCYTES

In vivo cell-mediated immune reactions are characterized by mixtures o f monocytes and T cells. The purpose of this study was to investigate the role of monocytes on T-cell migration and induction of endothelial adhesion molecules. The in vitro model consisted of adding peripheral blood mononuclear cells (PBMC), T cells or mixtures of monocytes and T cells, to endothelial cells on a porous membrane and using flow cyto metry to distinguish between the monocyte and lymphocyte components. P BMC and PBMC supernatants were highly potent at upregulating intercell ular adhesion molecule-1 (ICAM-1) and inducing expression of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Induction by superna tants was inhibited by antibodies to tumour necrosis factor-alpha (TNF -alpha) and interleukin-1 (IL)-1 beta. Using monocyte-enriched populat ions, as few as one monocyte to 100 endothelial cells was sufficient t o upregulate adhesion molecules. Fixed monocytes also induced adhesion molecules and expressed surface-bound cytokines. In contrast, highly purified unstimulated T cells were not found to induce adhesion molecu les at 4, 6, 24 or 48 hr of coculture. Purified T cells showed low-lev el migration through resting (VCAM-1 negative) endothelium, which was approximately doubled by addition of small numbers of monocytes or TNF -alpha. In conclusion, monocytes, via cell surface or released cytokin es play an essential role in allowing large-scale recruitment of T cel ls to inflammatory sites in vivo.