Prevention by thymectomy of tolerance induced by intrathymic injection of donor splenocytes

Surgery. 1993 Aug;114(2):183-9; discussion 189-90.


Background: We have recently demonstrated indefinite donor-specific cardiac allograft survival after the intrathymic injection of donor splenocytes and simultaneous injection of antilymphocyte serum (ALS) in a fully major histocompatibility complex-mismatched rat combination. In this study we performed thymectomy to determine the length of time required for donor alloantigen to be present in the recipient thymus to induce tolerance.

Methods: Male Buffalo (BUF; RT1b) rats at 4 to 8 weeks of age underwent intrathymic injection of 25 x 10(6) Lewis (LEW; RT1(1)) splenocytes and simultaneously received an intraperitoneal injection of 1 ml ALS. To determine the kinetics of tolerance induction, the BUF recipients underwent thymectomy on days 1, 3, or 7 after the initial intrathymic injection of alloantigen and intraperitoneal ALS. Twenty-one days after intrathymic alloantigen injection and ALS, all rats underwent transplantation with a heterotopic LEW cardiac allograft.

Results: Thymectomy performed 1 (mean survival time, 6.8 days) and 3 (mean survival time, 8.0 days) days after donor alloantigen injection and ALS did not affect the normal rejection of LEW cardiac allografts. In contrast, thymectomy 7 days after intrathymic alloantigen injection and ALS resulted in indefinite survival of cardiac allografts in 75% of recipients (mean survival time > 77.0 days). In addition, allospecific cytotoxic T lymphocyte activity and interleukin-2 production were markedly decreased in those recipients undergoing thymectomy after 7 days compared with untreated control rats and recipients undergoing thymectomy 1 and 3 days after alloantigen injection.

Conclusions: The presence of the thymus for at least 7 days after intrathymic alloantigen injection and intraperitoneal ALS allows the development of indefinite donor-specific cardiac allograft tolerance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antilymphocyte Serum / pharmacology
  • Heart Transplantation / immunology*
  • Immune Tolerance*
  • Immunotherapy, Adoptive*
  • Interleukin-2 / biosynthesis
  • Isoantigens / immunology*
  • Lymphocytes / immunology*
  • Male
  • Rats
  • Rats, Inbred ACI
  • Rats, Inbred BUF
  • Rats, Inbred Lew
  • Spleen / immunology
  • Thymectomy*
  • Thymus Gland / pathology
  • Transplantation, Homologous


  • Antilymphocyte Serum
  • Interleukin-2
  • Isoantigens