J.Jpn. Surg. Soc.. 97(12): 1097-1108, 1996

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Editorial

CYCLOPHOSPHAMIDE-INDUCED IMMUNOLOGICAL TOLERANCE: AN OVERVIEW

Acyclophosphamide (CP)-induced tolerance system in mice that primarily consists of donor cell injection followed by CP-treatment was found useful for inducing a long-lasting allo-or xeno-tolerance to various solid organs. In the cells-followed-by-CP system, the sequential mechanisms of the tolerance were clarified using the specific correlation between superantigens and certain T cell receptor (TCR) Vβ segments. Those include the clonal destruction of antigen-stimulated mature T cells, the peripheral clonal deletion associated with peripheral chimerism, the intrathymic clonal deletion associated with intrathymic chimerism, and the clonal anergy. The generation of suppressor T cells was another important mechanism of the tolerance in the late stage. Special care taken to overcome the “hard” barriers of alloor xeno-combinations by reducing the “split tolerance” produced through the clonal destruction mechanism. For this purpose, the tolerogen, antimitotic drug their doses, timing, route of administration, combined immunosuppressants, and supportive treatment were all crucial for successful induction of a long-lasting skin tolerance. This system may be applicable to human transplantation.

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