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 were responsible for the activity of B16 melanoma-specific cytotoxic T lymphocytes (CTL). The in vivo depletion of NK cells with anti-NK1.1 monoclonal antibody (mAb), prior to B16-immunization, significantly decreased the capacity of the spleen cells (s.c.) to generate B16-specific CTL after in vitro restimulation. However, the CD8+ T cells of the s.c. from NK cell-depleted and subsequently B16-immunized mice increased their potential to become B16-specific CTL compared with those from the B16-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 s.c. 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.
Terao
H
H
Department of Immunology, Kyushu University, Fukuoka, Japan.
Harada
M
M
Kurosawa
S
S
Shinomiya
Y
Y
Ito
O
O
Tamada
K
K
Takenoyama
M
M
Nomoto
K
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization / Q000379:methods*; D007156:Immunologic Memory / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured