Determination of the immune system that suppresses tumor formation of the tumor cybrids containing allogenic mtDNA. (A–F and H) The tumor cybrids were inoculated under the skin of B6 β2m^−/− and B6 Tap1^−/− mice (A), B6 Abβ^−/− mice (B), B6 Rag2^−/− mice (C), B6 Rag2^−/−/γc^−/− mice (D), B6 NK^Red mice (E), B6mtNZB NK^Red mice (F), and B6 Myd88^−/− and B6 Myd88^−/−/NK^Red mice (H) to study the involvement of the immune system and immune cells in the suppression of tumor formation (n = 6). Similar results were obtained in two independent experiments. Error bars represent SD. (G) Contribution of perforin but not FasL in preferential killing of P29mtNZB by NK cells derived from B6 Rag2^−/− mice. Cytotoxic assay of B6 Rag2^−/− splenocytes that had been stimulated with poly I:C in vivo for 20 h was tested against P29mtB6 or P29mtNZB at the indicated E/T ratios. An 8-h ⁵¹Cr releasing assay was performed in the presence or absence of 20 nM concanamycin A or 10 µg/ml anti-FasL antibody. In all experiments, spontaneous ⁵¹Cr release from the P29 cybrids was <15%. Data represent the mean ± SD of triplicate samples. Similar results were obtained in two independent experiments (*, P < 0.0005; **, P < 0.0001).