ADOPTIVE CELL TRANSFER OF CONTACT SENSITIVITY-INITIATION MEDIATED BY NONIMMUNE CELLS SENSITIZED WITH MONOCLONAL IGE ANTIBODIES - DEPENDENCEON HOST SKIN MAST-CELLS

A role for mast cell release of serotonin (5-HT), via Ag-specific fact ors derived from Thy-1(+) B220(+) lymphoid cells in the initiation of murine contact sensitivity (CS) has been suggested. However, because C S in mast cell-deficient mice was intact, a role for mast cells in CS initiation was unclear. Therefore, we examined whether CS could be ini tiated by i.v. injection of nonimmune mixed lymphoid cells that were s ensitized in vitro with IgE. When naive mice received IgE-sensitized n onimmune spleen or lymph node cells, or IgE-sensitized purified mast c ells, together with immune CS-effector B220(-) T cells, which therefor e were depleted of CS-initiating, Thy-1(+), B220(+) cells, which could not transfer CS, then reconstitution of CS occurred. Mast cell-deiici ent W/W-v mice could not elicit this IgE-dependent CS ear swelling, bu t when mast cell deficiency was reversed by ear injection of normal bo ne marrow-derived cultured mast cells, then CS was restored. In vitro pretreatment with irrelevant monoclonal anti-OVA IgE prevented CS init iation mediated by Ag-specific, IgE mAb-sensitized cells, presumably b y blocking sensitization with IgE. Thus Fc epsilon R on the normal lym phoid cells were involved. When ketanserin, a 5-HT2 receptor antagonis t, was injected i.v. before cell transfer, CS initiation via IgE-sensi tized cells and CS were no longer elicited. Thus, in this system, IgE Abs bound to circulating IgE Fc epsilon R bearing lymphoid cells sensi tized in vitro (most likely basophils), probably mediated early activa tion of these circulating basophils to release mediators, causing 5-HT release from cutaneous mast cells, to mediate CS initiation.