ALTERED TARGET ORGAN - A MECHANISM OF POSTRECOVERY RESISTANCE TO MURINE AUTOIMMUNE OOPHORITIS

Experimental murine autoimmune oophoritis, a model of human premature ovarian failure, is induced by immunization with a peptide of the ZP3 glycoprotein from mouse zona pellucida (Zp3(330-340)) in CFA. The ovar ian pathology is mediated by ZP3-specific, CD4(+) T cells, and not by Abs. We now show that mice recovered from autoimmune oophoritis in 4 m o, as characterized by regression of ovarian inflammation. Recovery wa s associated with disease resistance upon rechallenge with ZP3(330-340 ) in CFA. Oophoritis resistance was not explicable by immunosuppressiv e effect of CFA priming, nor by suppression of pathogenic T cells. ZP3 -specific, proliferative T cell response could be detected, and a ZP3- specific, IFN-gamma-producing pathogenic T cell line was derived readi ly from the recovered mice by in vitro stimulation with the Zp3(330-34 0) peptide. Moreover, recovered mice, when challenged with ZP3(330-340 ) in CFA, produced Abs of IgG class to the Zp3(330-340) peptide. Suppr essor T cells are not readily demonstrable. Most importantly, oophorit is occurred in normal ovaries implanted under the renal capsule of the recovered mice. That oophoritis developed in the implanted ovaries, b ut spared the endogenous ovaries, further indicates that the latter is refractory to oophoritis. Disease resistance of the ovaries is not ex plicable by limitation of accessible target Ags. When mated, recovered mice were fertile and produced normal litters; and, as recipients of a ZP3-specific T cell line, their ovaries developed oophoritis. We con clude that altered local environment of the target organ following aut oimmune disease recovery can contribute to the complex disease-resista nt state.