Heat-stable antigen is an important costimulatory molecule on epidermal Langerhans' cells

Heat-stable antigen (HSA), expressed by activated B cells, has been described as a costimulatory molecule for CD4+ T cells. Because epidermal Langerhans cells (LC) are known to express HSA, we determined whether LC HSA also served as a costimulator of Th cells. We have confirmed that HSA is expressed by freshly prepared (fresh) and, to a lesser extent, short-term cultured (cultured) LC and we demonstrate that costimulatory effects of HSA are prominent on fresh and 1-day cultured LC, whereas 2- to 4-day cultured LC exhibit less HSA-costimulatory activity. The anti-HSA mAb 20C9 almost completely blocked the proliferative response of Th1 or lymph node T cells induced by fresh or cultured LC. 20C9 also specifically inhibited LC-dependent IL-2 production by Th1 cells. The inhibitory effect of 20C9 was not observed when Th2 cells were substituted for Th1 cells or peripheral lymph node T cells. Furthermore, Th1 cells rescued from cocultures of T cells and 20C9-treated, Ag-pulsed LC, (but not from control-treated cocultures) were anergic to restimulation with untreated Ag-pulsed LC. These data suggest that LC HSA is an important costimulatory molecule in Th1 cell-dependent cutaneous immune reactions.