T-cell activation, proliferation, and memory after cardiac transplantation in vivo

Ann Surg. 1999 Apr;229(4):570-8. doi: 10.1097/00000658-199904000-00018.


Objective: To study the response of alloantigen (H2Kb)-specific T cells to a H2b+ cardiac allograft in vivo.

Summary background data: The response of T cells to alloantigen has been well characterized in vitro but has proved more difficult to assess in vivo. The aim of these experiments was to develop a model of T-cell-mediated rejection where the response of T cells after transplantation of a cardiac allograft could be followed in vivo.

Methods: Purified CD8+ T cells from H2Kb-specific TCR transgenic mice (BM3; H2k) were adoptively transferred into thymectomized, T-cell-depleted CBA/Ca (H2k) mice. These mice were then transplanted with a H2Kb+ cardiac allograft. Using four-color flow cytometry, the proliferative response, modulation of activation markers, and potential cytokine production of the H2Kb-specific T cells was assessed after transplantation.

Results: Consistent rejection of H2Kb+ cardiac allografts required the transfer of at least 6 x 10(6) CD8+ H2Kb-specific T cells. Short-term analyses revealed that the transgenic-TCR+/ CD8+ T cells proliferated and became activated after transplantation of an H2Kb+ cardiac allograft. Fifty days after transplantation, the transgenic-TCR+/CD8+ T cells remained readily detectable, bore a predominantly memory phenotype (CD44hi), and rapidly produced interleukin 2 and interferon-gamma on in vitro restimulation.

Conclusions: These data show that the activation of alloantigen-specific T cells can be followed in vivo in short-term and long-term experiments, thereby providing a unique opportunity to study the mechanisms by which T cells respond to allografts in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Cell Division
  • Heart Transplantation / immunology*
  • Immunologic Memory*
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Receptors, Antigen, T-Cell / biosynthesis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Receptors, Antigen, T-Cell