Abstract：
:A cyclophosphamide (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 tolerance were clarified using the specific correlation between superantigens and certain T cell receptor (TCR) V beta 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 tolerance in the late stage. Special care was taken to overcome the " hard" barriers of allo- or xeno-combinations by reducing the "split tolerance" produced through the clonal destruction mechanism. For this purpose, the tolerogen, antimitotic drugs, 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.
journal_name
Immunobiologyjournal_title
Immunobiologyauthors
Mayumi H,Umesue M,Nomoto Kdoi
10.1016/S0171-2985(96)80033-7subject
Has Abstractpub_date
1996-07-01 00:00:00pages
129-39issue
2eissn
0171-2985issn
1878-3279pii
S0171-2985(96)80033-7journal_volume
195pub_type
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