Accessory function for NK1.1+ natural killer cells producing interferon-gamma in xenospecific cytotoxic T lymphocyte differentiation.
| Autor: | Smyth MJ; Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Victoria, Australia., Kelly JM |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Transplantation [Transplantation] 1999 Sep 27; Vol. 68 (6), pp. 840-3. |
| DOI: | 10.1097/00007890-199909270-00017 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|