Accessory function for NK1.1+ natural killer cells producing interferon-gamma in xenospecific cytotoxic T lymphocyte differentiation

Transplantation. 1999 Sep 27;68(6):840-3. doi: 10.1097/00007890-199909270-00017.


Background: We have previously demonstrated that xenospecific cytotoxic T lymphocyte (CTL) differentiation requires accessory function by NK1.1+ cells, yet the mechanism by which NK1.1+ cells support CTL generation had not been elucidated.

Methods: An established model in which mice generate a strong local popliteal lymph node CTL response to footpad immunizations with human tumor cells was used. Mice depleted of NK1.1+ cells fail to mount a maximal xenospecific CD8+ CTL response. The xenospecific CTL response in anti-NK1.1 monoclonal antibody-depleted mice could be completely restored if mice were coinoculated with human tumor cells (the xenoantigen) and xenoantigen-stimulated syngeneic natural killer (NK) cells from wild-type or perforin-deficient mice. By contrast, NK1.1+ cells from interferon-gamma-deficient mice did not restore the maturation of xenospecific CTL in anti-NK1.1 monoclonal antibody-treated mice. Depletion of NK1.1+ cells in vivo from both wild-type and Jalpha281-deficient mice (which lack Valpha14 NK1.1+ T cells) abrogated the generation of xenospecific CTL, however, untreated Jalpha281-deficient mice mounted a normal xenogeneic response.

Conclusions: These data indicate that local NK cell production of interferon-gamma at the site of challenge is an important stimulus for generating xenospecific CTL in local draining lymph nodes and that Valpha14 NK T cells play little or no regulatory function in this response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Specificity
  • Cell Differentiation / immunology
  • Humans
  • Interferon-gamma / biosynthesis*
  • Jurkat Cells
  • Killer Cells, Natural / metabolism*
  • Mice
  • T-Lymphocytes, Cytotoxic / cytology*
  • Transplantation, Heterologous / immunology


  • Interferon-gamma