Ontogeny of the alloimmune response against a transplanted tumor in Xenopus laevis

Xenopus laevis lymphoid tumor cells of the ff genotype grow after transplantation in inbred ff tadpoles or young post-metamorphic animals, but do not grow in fully grown ff adults. The ability to grow is lost progressively after metamorphosis and is apparently due to an immune response of the adult host against minor histocompatibility antigens (non-MHC encoded) expressed by the tumor cells. The difference in alloimmune responses between the larval and the adult immune system of the amphibian Xenopus has been subsequently investigated with this new in vivo model. The resistance of the host against transplanted tumor cells rises during the post-metamorphic development in parallel with the second histogenesis observed in the thymus, the expression of MHC class II by peripheral T cells and the recovery of T cell effector functions such as MLR, and can be abrogated by sub-lethal irradiation. Pre-immunization of ff adults with irradiated ff-2 cells specifically accelerates subsequent ff skin graft rejection, which implies the generation of memory against antigenic determinants common between the ff skin and the tumor cells. Similarly, both anti-ff alloserum and anti-ff-2 serum contain antibodies specifically precipitating two surface proteins (180-200 kDa) from ff-2 cells. One of these proteins is also detected on normal ff thymocytes and splenic T cells. On the other hands, ff-2 tumor cells (MHC I+II-) are not rejected by class I-negative tadpoles (class I expression on the tumor cell surface is even increased), and no anti-tumor antibody response can be detected. However, tumor growth has been reduced in tadpoles following priming with irradiated ff-2 cells, although immunization is not sufficient to prevent ultimate tumor development and tadpole death. Moreover, priming with irradiated ff-2 cells at larval stages does interfere with tumor growth in transplanted young post-metamorphic adults, suggesting that long-lived memory has been generated and has been maintained through metamorphosis. These results suggest that the lack of tumor rejection by larvae results from an incomplete effector function rather than an absence of recognition. Full responsiveness against minor H antigens cannot be elicited before adulthood.