Visualization of the in vivo generation of donor antigen-specific effector CD8+ T cells during mouse cardiac allograft rejection: in vivo effector CD8+ T cell generation during allograft rejection

Transplantation. 2000 Feb 27;69(4):639-48. doi: 10.1097/00007890-200002270-00028.

Abstract

Background: An adoptive transfer system was used to study the fate of alloreactive CD8+ H-2Kb-specific TCR transgenic (DES+) T cells in vivo after transplantation.

Methods: A trace population of 2.0x10(6) CD8+DES+ T cells were adoptively transferred into syngeneic CBA.Ca (H-2k) mice 24 hr before transplantation of an H-2Kb+ or H-2Kb- cardiac allograft.

Results: H-2Kb specific T cells proliferated and produced interleukin-2 and interferon-gamma in response to H-2Kb+, but not H-2Kb- cardiac allografts. CD8+DES+ T cells that infiltrated the H-2Kb+ cardiac allografts developed a distinct cell surface and cytokine phenotype compared with the CD8+DES+ T cells that remained in the periphery. H-2Kb-specific graft infiltrating T cells (a) underwent a larger number of cell divisions (> =3), (b) increased in size, (c) up-regulated CD69, and (d) down-regulated CD62L.

Conclusions: These results demonstrate that alloantigen-specific T cells can be monitored in vivo during the immune response to an allograft and that the fate of CD8+ T cells specific for the allogeneic class I molecules expressed by the graft is different between cells in the periphery and those that infiltrate the graft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods
  • Animals
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Division / immunology
  • Cytokines / biosynthesis
  • Epitopes
  • Flow Cytometry
  • Graft Rejection / metabolism
  • Graft Rejection / pathology
  • Graft Survival / immunology
  • Heart Transplantation / immunology*
  • Histocompatibility Antigens Class I / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / drug effects
  • Ionomycin / pharmacology
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tissue Donors
  • Transplantation, Homologous / pathology

Substances

  • Cytokines
  • Epitopes
  • Histocompatibility Antigens Class I
  • Ionomycin
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate