Accessory function for NK1.1+ natural killer cells producing interferon-gamma in xenospecific cytotoxic T lymphocyte differentiation.
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.
Smyth
M J
MJ
Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Victoria, Australia.
Kelly
J M
JM
D000818:Animals; D000918:Antibody Specificity; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000378:metabolism*; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*; D014183:Transplantation, Heterologous / Q000276:immunology
D007371:Interferon-gamma