The opposite effect of tumor-infiltrating natural killer cells on in vivo priming of tumor-specific CD8⁺ T cells and CD4⁺ T cells

Natural killer (NK) cells, which infiltrated the tumor site, were examined for their effects on the in vivo priming of tumor-specific CD8⁺ and CD4⁺ T cells. CD8⁺ T cells mere responsible for the activity of B16 melanoma-specific cytotoxic T lymphocytes (CTL). The in vivo depletion of NK cells with anti-NR1.1 monoclonal antibody (mAb), prior to B16-immunization, significantly decreased the capacity of the spleen cells (SC) to generate B16-specific CTL after in vitro restimulation. However, the CD8⁺ T cells of the SC from NK cell-depleted and subsequently B16-immunized mice increased their potential to become B16-specific CTL compared with those from the Bib-immunized mice. The tumor-infiltrating NK cells showed a low but significant degree of CTL activity against B16. In addition, the disrupted B16 melanoma cells demonstrated less of an ability to in vivo prime the tumor-specific CD8⁺ T cells. These findings thus suggest the possibility that the quick disruption of tumor cells by tumor-infiltrating NK cells consequently interfered with the in vivo priming of the tumor-specific CD8⁺ T cells. On the other hand, the CD4⁺ T cells of the SC from NK cell-depleted and subsequently B16-immunized mice showed less of a capacity to induce the tumor-specific CTL compared with those from B16-immunized mice. In addition, the delayed-type hypersensitivity response against B16 was significantly diminished by the in vivo depletion of NK cells prior to B16-immunization. These findings thus suggest that NK cells have a promoting effect on the in vivo priming of CD4⁺ T cells. Overall, however, our findings indicate that early-appearing tumor-infiltrating NK cells have an opposite effect on the in vivo priming of CD8⁺ and CD4⁺ T cells.