ROLE OF X-LINKED IMMUNODEFICIENCY (XID) AND NK ACTIVITY IN REJECTION OF HUMAN TUMOR XENOTRANSPLANTS IN NUDE-MICE

In order to elucidate the factors influencing the takes of human tumor xenografts in nude mice, we compared the transplantability of human t umors in nude mice with additional genetic defects in the immune syste m. The nude mice strains tested were classified as follows by expressi on of the beige gene and the x-linked immunodeficiency (xid) gene: 1) high NK nude (C57BL/6N, nu/nu), 2) low NK nude (C57BL/6 bg/bg nu/nu), 3) high NK nude with B-cell defect (CBA/N nu/nu), and 4) low NK nude w ith B-cell defect (NIH(S)III). Takes of human tumor xenografts includi ng gastric carcinoma, T-cell lymphoma and B-cell lymphoma were better in nude mice with xid (CBA/N and NIH(S) III nude mice) than in nude mi ce without xid (B6 and beige nude mice). In addition, among the nude m ice with xid expression, the takes were slightly better in nude mice w ith a CBA/N background than in those with a NIH(S) background. Moreove r, the xenotransplantation rate in (CBA/N x C57BL/6N)F1 male nude mice with xid expression was higher than in (C57BL/6N x CBA/N)F1 males wit hout xid expression, but did not react the same level as that in CBA/N nude. On the other hand, introduction of the beige gene into nude mic e minimally improved the takes of human tumor xenografts under limited experimental conditions (inoculation of 100 x 10(5) T-cell lymphoma a nd 1 x 10(5) gastric carcinoma cells) despite the reduction of NK acti vity. In xenotransplantation of human tumors directly from patients, t he take rates of the tumors were also better in CBA/N nude mice than i n BALB/cA nude mice. The results in the present report confirmed the e ffect of xid and CBA/N genetic background on human tumor xenografts in nude mice, suggesting the existence of serum factors, possibly presen t in serum IgM, mediating rejection of the xenografts.