The requirement of intrathymic mixed chimerism and clonal deletion for a long‐lasting skin allograft tolerance in cyclophosphamide‐induced tolerance

Masatoshi Eto, Hisanori Mayumi, Yasunobu Yoshikai, Yousuke Nishimura, Kikuo Nomoto

Research output: Contribution to journalArticle

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Abstract

Mechanisms of cyclophosphamide (CY)‐induced tolerance were studied. When C3H/He Slc (C3H; H‐2k, Mls‐1b) mice were primed i.v. with 1 × 108 viable spleen cells from H‐2‐identical AKR/J Sea (AKR; H‐2k, Mls‐1a) mice and treated with 200 mg/kg of CY 2 days later, a long‐lasting skin allograft tolerance to AKR was established. When [C57BL/6 Sea (B6; H‐2b, Mls‐1b) × AKR]F1 (B6AKF1) cells were used as the tolerogen, however, only a moderate, but not long‐lasting, skin tolerance to AKR was observed. In the C3H mice treated with AKR cells and CY, the intrathymic clonal deletion of Vβ6+ T cells, which are strongly correlated with reactivity to Mls‐1a antigens, was observed in the chimeric thymus on day 35, although neither the clonal deletion of Vβ6‐bearing T cells nor the mixed chimerism was observed in the thymus on day 14. In the C3H mice treated with B6AKF1 cells followed by CY, however, neither the clonal deletion of Vβ6+ T cells nor the mixed chimerism was observed in the thymus throughout the test period. In the lymph nodes of the C3H mice treated with AKR cells and CY, only CD4+Vβ6+ T cells, but not CD8+Vβ6+ T cells, had selectively decreased by day 14, and they were hardly detectable on day 35. The selective decrease of CD4+Vβ6+ T cells in the lymph nodes was also observed by day 14 when B6AKF1 cells were used as the tolerogen, although CD4+Vβ6+ T cells gradually increased on day 35, at which time almost all skin grafts from AKR had already been rejected. These results strongly support the necessity of the intrathymic mixed chimerism and clonal deletion of donor‐reactive T cells for a long‐lasting skin allograft tolerance in CY‐induced tolerance.

Original languageEnglish
Pages (from-to)2005-2013
Number of pages9
JournalEuropean Journal of Immunology
Volume20
Issue number9
DOIs
Publication statusPublished - Sep 1990

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Clonal Deletion
Transplantation Tolerance
Chimerism
T-Lymphocytes
Skin
Cyclophosphamide
Oceans and Seas
Inbred C3H Mouse
Thymus Gland
Lymph Nodes
Spleen
Transplants
Antigens

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

The requirement of intrathymic mixed chimerism and clonal deletion for a long‐lasting skin allograft tolerance in cyclophosphamide‐induced tolerance. / Eto, Masatoshi; Mayumi, Hisanori; Yoshikai, Yasunobu; Nishimura, Yousuke; Nomoto, Kikuo.

In: European Journal of Immunology, Vol. 20, No. 9, 09.1990, p. 2005-2013.

Research output: Contribution to journalArticle

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