Role of Peripheral Hemopoietic Chimerism in Achieving Donor-Specific Tolerance in Adult Mice

Takeshi Maeda, Masatoshi Eto, Yousuke Nishimura, Kenichi Nomoto, Young Yun Kong, Kikuo Nomoto

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37 Citations (Scopus)


The role of peripheral hemopoietic chimerism in the induction and maintenance of donor-specific tolerance was investigated by our tolerance-inducing method using cyclophosphamide (CP). As has been previously reported, CP injection at a dose of 200 mg/kg to C3H (Thy-1.2, Mls-1b) mice 2 days after priming with 108 viable AKR (Thy-1.1, Mls-1a) spleen cells (SC) resulted in both establishment of mixed chimerism and selective elimination of Vβ6+CD4+ T cells in the periphery. When, instead of viable SC, 1300 rad irradiated 108 AKR SC were used for priming to C3H mice, CP treatment 2 days after the priming also caused significant but, as compared with priming with nonirradiated viable cells, incomplete elimination of Vβ6+ T cells in the periphery. In these mice, no hemopoietic chimerism was found. In parallel with this incomplete elimination of peripheral Vβ6+ T cells, LN cells of these mice showed reduced but considerable response to AKR SC. However, once hemopoietic chimerism was introduced to these incompletely tolerant mice by an injection with donor-type viable [AKR × C3H]F1 SC 2 days after CP-treatment, LN cells from these newly established chimeras, irrespective of presence or absence of the thymus, became completely nonresponsive to AKR while preserving normal response to BALB/c (third party). This state of nonresponsiveness was accompanied by clonal elimination of the remaining Vβ6+ T cells in the periphery. These results indicate that peripheral chimerism promoted profound tolerance to donor-Mls Ag specifically. Furthermore, from experiments of skin grafting, we demonstrated that tolerance to minor histocompatibility Ag was also achieved in the presence of peripheral hemopoietic chimerism. Journal of Immunology, 1993, 150: 753.

Original languageEnglish
Pages (from-to)753-762
Number of pages10
JournalJournal of Immunology
Issue number3
Publication statusPublished - 1993

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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