ANTIGEN-INDUCED UNRESPONSIVENESS IN CONTACT SENSITIVITY - ASSOCIATIONOF DEPRESSED T-LYMPHOCYTE PROLIFERATIVE RESPONSES WITH DECREASED INTERLEUKIN-6 SECRETION

Topical exposure of mice to the contact allergen oxazolone induces bot h a persistent antigen-specific down-regulation of subsequent lymph no de cell (LNC) proliferative responses stimulated by the same chemical and a more transient depression of LNC proliferative responses provoke d by exposure to unrelated chemical sensitizers; the latter being asso ciated with antigenic competition in contact sensitivity. In this pape r a relationship between reduced LNC proliferative activity and the se cretion of interleukin 6 (IL-6) is described. Pretreatment of mice wit h oxazolone caused a persistent, dose-dependent inhibition of LNC prol iferative activity and a parallel reduction of IL-6-secretion when mic e were Ie-exposed, at a different site, to the same chemical. Consiste nt with dendritic cells (DC) being the major source of IL-6 within all ergen-activated lymph nodes, depletion of Thy-1(+) T lymphocytes did n ot compromise production of this cytokine. Although in mice pretreated with oxazolone IL-6 secretion by cultured LNC was impaired markedly, the initial IL-6 content of freshly isolated LNC was apparently normal . These data suggest that the down-regulation of lymphocyte proliferat ive responses induced by exposure of mice to oxazolone, and the conseq uential impaired responsiveness, is associated with, and possibly seco ndary to, the reduced secretion by lymph node DC of IL-6, a cytokine t hat is a costimulator of T lymphocyte activation and the production of which correlates closely with the vigour of LNC proliferative activit y.