Importance of intrathymic mixed chimerism for the maintenance of skin allograft tolerance across fully allogeneic antigens in mice

M. Eto, Y. Y. Kong, J. Uozumi, S. Naito, K. Nomoto

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

In B6 (H-2b) mice that had been given, neonatally, 1 x 108 B6AKF1 spleen cells intraperitoneally (i.p.), only a moderate prolongation of donor (AKR: H-2(k)) skin graft survival was observed. In such B6 mice, no mixed lymphocyte reaction (MLR) to AKR could be detected on day 35 (35 days after birth), but it was clearly evident on day 84. Similarly, neither Vβ6+ (reactive to MTV-7-encoded antigens) nor Vβ11+ (reactive to I-E + MTV- derived superantigens) T cells were detected on day 35, but both were clearly evident on day 84 in both the thymus and the lymph nodes, thus indicating the breakdown of intrathymic mixed chimerism at the antigen-presenting cell level. Furthermore, by day 84, all skin grafts from AKR had already been rejected in such B6 mice. In the periphery, however, Vβ6+, but not Vβ11+, T cells were clonally anergic on day 84, based on a stimulation assay with anti-T-cell receptor (TCR) monoclonal antibody (mAb), thus suggesting that tolerance to some antigens, but not to others, may be induced by the clonal anergy in fully allogeneic combinations, and that the clonal anergic state may be masked by other proliferative responses. These results therefore indicate the importance of intrathymic mixed chimerism (central tolerance) and the limitations of clonal anergy (peripheral tolerance) in maintaining tolerance across fully allogeneic antigen barriers.

Original languageEnglish
Pages (from-to)440-446
Number of pages7
JournalImmunology
Volume96
Issue number3
DOIs
Publication statusPublished - 1999

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Importance of intrathymic mixed chimerism for the maintenance of skin allograft tolerance across fully allogeneic antigens in mice'. Together they form a unique fingerprint.

  • Cite this