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The Journal of Immunology, 1998, 160: 3086-3090.
Copyright © 1998 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Multiple Mechanisms of Peripheral T Cell Tolerance to the Fetal "Allograft"

Shi-Ping Jiang1 and Melanie S. Vacchio2

Laboratory of Immunology, Division of Hematologic Products, Center for Biologics Evaluation Research and Review, U.S. Food and Drug Administration, Bethesda, MD

The fetus represents a foreign entity to the maternal immune system, yet this "natural" allograft is not normally rejected. This unique situation provides a physiologic system to evaluate peripheral tolerance in which the maternal immune system is challenged with relatively rare Ags not previously encountered in the thymus. Using H-Y-specific TCR transgenic mice, we demonstrate that T cells specific for fetal Ags decrease in an Ag-specific manner during pregnancy and remain low postpartum, the result of an encounter with fetal cells expressing the appropriate MHC/peptide complexes. The finding that placental trophoblasts can induce Fas-mediated death of T cells is consistent with peripheral clonal deletion as one mechanism of tolerance. The remaining clonotypic T cells are unresponsive to antigenic stimulation, although neither TCR nor coreceptor is down-regulated. Our study demonstrates that specific recognition of fetal allogeneic Ags by maternal T cells results in tolerance induction of reactive T cells via multiple mechanisms.




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