Specific destruction of host-reactive mature T cells of donor origin prevents graft-versus-host disease in cyclophosphamide-induced tolerant mice

M. Eto, H. Mayumi, Y. Tomita, Y. Yoshikai, Y. Nishimura, T. Maeda, T. Ando, K. Nomoto

Research output: Contribution to journalArticle

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Abstract

In cyclophosphamide (CP)-induced tolerance, a long lasting skin allograft tolerance was established in many H-2-identical strain combinations without graft vs host disease. Destruction of donor-reactive T cells of host origin, followed by intrathymic clonal deletion of these cells, has been revealed to be the chief mechanisms of this system. Here, we studied the fate of host-reactive populations in donor-derived T cells of C3H/He (C3H) (H-2(k), Mls- 1b, Mls-2a) mice rendered CP-induced tolerant to AKR/J (AKR) (H-2(k), Mls-1a, Mls-2b), by assessing AKR-derived Thy-1.1+ T cells bearing TCR Vβ3 that are specifically reactive with Mls-2a-encoded Ag of the recipient C3H mice. In the AKR-derived Thy-1.1+ lymph node cells of the C3H mice that had been treated with AKR spleen cells plus CP, CD4+-Vβ3+ T cells were obviously decreased by day 10 after the CP treatment. At this stage, the Thy-1.1+ T cells were not detected in the C3H thymus, suggesting that the obvious decrease of CD4+-Vβ3+ T cells of AKR origin was not due to intrathymic clonal deletion in the recipient C3H mice. Therefore, the destruction of the host-reactive mature T cells of donor origin, as well as that of the donor-reactive mature T cells of host origin, occurred by the CP treatment at the induction phase. Furthermore, after the establishment of intrathymic mixed chimerism in the recipient C3H mice, Vβ3+ T cells were not detected among the Thy-1.1+ T cells of AKR origin in the mixed chimeric thymus, suggesting that the host-reactive immature T cells repopulated from the injected donor hematopoietic cells were clonally deleted in the recipient thymus. These two mechanisms appear to prevent graft vs host disease in CP-induced tolerance.

Original languageEnglish
Pages (from-to)1402-1409
Number of pages8
JournalJournal of Immunology
Volume146
Issue number5
Publication statusPublished - Jan 1 1991

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Graft vs Host Disease
Cyclophosphamide
T-Lymphocytes
Inbred C3H Mouse
Clonal Deletion
Thymus Gland
Transplantation Tolerance
Chimerism
Spleen
Lymph Nodes
Skin

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Specific destruction of host-reactive mature T cells of donor origin prevents graft-versus-host disease in cyclophosphamide-induced tolerant mice. / Eto, M.; Mayumi, H.; Tomita, Y.; Yoshikai, Y.; Nishimura, Y.; Maeda, T.; Ando, T.; Nomoto, K.

In: Journal of Immunology, Vol. 146, No. 5, 01.01.1991, p. 1402-1409.

Research output: Contribution to journalArticle

Eto, M, Mayumi, H, Tomita, Y, Yoshikai, Y, Nishimura, Y, Maeda, T, Ando, T & Nomoto, K 1991, 'Specific destruction of host-reactive mature T cells of donor origin prevents graft-versus-host disease in cyclophosphamide-induced tolerant mice', Journal of Immunology, vol. 146, no. 5, pp. 1402-1409.
Eto, M. ; Mayumi, H. ; Tomita, Y. ; Yoshikai, Y. ; Nishimura, Y. ; Maeda, T. ; Ando, T. ; Nomoto, K. / Specific destruction of host-reactive mature T cells of donor origin prevents graft-versus-host disease in cyclophosphamide-induced tolerant mice. In: Journal of Immunology. 1991 ; Vol. 146, No. 5. pp. 1402-1409.
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AU - Nishimura, Y.

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AU - Ando, T.

AU - Nomoto, K.

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