THYMIC LYMPHOMAS IN INTERLEUKIN-9 TRANSGENIC MICE

Transgenic mice overexpressing the interleukin 9 gene were generated t o study the biological activity of this cytokine in vivo. Although no major histological or morphological modifications of the lymphoid syst em were observed in most animals, similar to 7% of transgenic mice dev eloped thymic lymphomas at the age of 3-9 months. The tumor cells, whi ch were clonal, with unique T cell rearrangements, were double positiv e for the expression of CD4 and CD8. The need for additional transform ing events, suggested by the low incidence of spontaneous tumors, was further indicated by the high susceptibility of the transgenic animals to injections of low doses of N-methyl-N-nitrosourea, a chemical carc inogen with a thymic tropism. Expression of interleukin 9 was required for optimal tumor growth in vivo, as one of the tumors studied, which had lost the transgene, was much more efficiently transplanted into t ransgenic than in normal mice. Moreover, the in vitro proliferative ac tivity of interleukin 9 on cell lines derived from such transgene-nega tive tumors suggests that an autocrine loop mediates the proliferation of these cells in vivo. Taken together, these results indicate that d ysregulated IL-9 expression could be involved in the development of so me T cell malignancies.