CYTOKINES AND ADHERENCE MOLECULES INVOLVED IN SPONTANEOUS DENDRITIC CELL-LYMPHOCYTE CLUSTERING IN SKIN AFFERENT LYMPH

The skin afferent lymph dendritic cell(DC) spontaneously forms clusters with autologous T cells. The role of adhesion molecules and cytokines in this process was investigated. Analysis of the expression of adhesion receptors on the canine peripheral lymph DC revealed the presence of CD54, CD58, CD18 as well as CD49d and CD49e molecules and cell surface fibronectin. The CD54 and CD58 molecules were found to play a key role in the 'spontaneous' lymph cell clustering. Antibody against fibronectin, a substrate for CD49d and CD49e receptors, reduced DC-lymphocyte binding. Analysis of the effect of cytokines revealed that the pro-inflammatory IL1 beta rather than IL1 alpha, and TNF alpha may be responsible for the enhanced lymph cell in vitro clustering. The IL6 had no such augmenting effect. The enhancing effect of endogenous IL1 beta present in lymph was reduced by the IL1 beta neutralizing antibody. The effect of exogenously added IL1 beta was also limited by the IL1 receptor antagonist. The IL1Ra alone had no effect on cell binding, even when used in the high doses. Neutralizing of IL1Ra in lymph with the specific antibody brought about augmented cluster formation. The enhancing properties of TNF alpha on cell binding were reduced by the TNF alpha neutralizing antibody. The IL10 significantly limited lymph DC cluster formation with T cells. In conclusion, these data demonstrate that the present in lymph IL1 beta and TNF alpha may be responsible for the observed ia vitro enhanced cluster formation of lymph DC with autologous T lymphocytes. Cell binding can be reduced by IL1Ra and by IL10. It provides insight into the potential clinical use of these inhibitors.