The effect of cytokines and chemotactic agonists on the migration of T lymphocytes into skin.

The migration of lymphocytes and neutrophils into skin sites stimulated with chemotactic agonists or with cytokines known to induce leucocyte-endothelial adhesion molecules was examined in sheep. Lymphocytes, collected from efferent prefemoral lymph, labelled in vitro with [111In]oxine and reinjected intravenously, migrated in large numbers into delayed-type hypersensitivity (DTH) reactions elicited by purified protein derivative (PPD) and into sites stimulated with tumour necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma). In contrast, interleukin (IL)-1 alpha, a potent inducer of endothelial leucocyte adhesion molecule-1 (ELAM-1), caused moderate accumulation of [111In]lymphocytes at concentrations that induced intense accumulation of 111In-labelled neutrophils. The chemotactic agonists IL-8 and zymosan-activated plasma (ZAP) caused accumulation of very large numbers of neutrophils but only small numbers of lymphocytes, whereas platelet-activating factor (PAF) and leukotriene B4 (LTB4) failed to recruit lymphocytes into skin. IFN-gamma was the only mediator to recruit lymphocytes in preference to neutrophils into skin. The results suggest that those lymphocyte chemotactic agonists which lack the ability to induce adhesion molecules on endothelium play only a minor role in directing migration of lymphocytes into skin. Immunohistological examination of skin lesions confirmed the findings of studies with 111In-labelled lymphocytes and indicated that there was a tendency for CD4+ cells to outnumber CD8+ cells in infiltrates induced by all mediators. In contrast to the elevated numbers of T19+ subset of T-cell receptor (TcR+) gamma delta cells present in DTH reactions, none of the mediators induced migration of T19+ cells into skin.