Tumor-induced suppression of interferon-γ production and enhancement of interleukin-10 production by natural killer (NK) cells: paralleled to CD4+ T cells

The predominance of type two cytokines in syngeneic B16 tumor-bearing mice was confirmed by analysing supernatant contents and mRNA copies of IFN-γ, IL-4, IL-5, IL-10 and IL-13 from splenocytes. The cytokine-producing lymphocytes were then examined by double-staining flowcytometry. Both CD4+IFN-γ+ T cells and DX5+IFN-γ+ NK cells from spleen significantly declined, interestingly, the declining degrees of DX5+IFN-γ+ NK cells were much greater than those of CD4+IFN-γ+ T cells by the percentage in whole NK or T cells or the absolute amounts per spleen at early tumor stage (day 10) or tumor-advanced stage (day 20). In contrast to DX5+IFN-γ+ NK cells, DX5+IL-10+ NK cells increased during tumor progression, the increasing degrees of DX5+IL-10+ NK cells were also much greater than those of CD4+IL-10+ T cells by the percentage or the absolute amounts. Though the percentage of DX5+IL-4+ NK cells only increased in early tumor stage (day 10), the increasing degree was also greater than that of CD4+IL-4+ T cells. In 20 × field view under laser confocal microscope, the mean numbers of DX5+IFN-γ+ NK cells and CD4+IFN-γ+ T cells dramatically declined after tumor inoculation. These results suggest that cytokines produced by NK cells, at least partly, account for the balance of type one and two cytokines as done by T cells, and in some conditions, that the NK1 or NK2 cells were possibly more sensitive to tumor progression.