Lymphoid hyperplasia in transgenic mice over-expressing a secreted form ofthe human interleukin-1 beta gene product

To evaluate the biological effects of over-expression of interleukin-1 beta (IL-1 beta) on the immune system we have generated transgenic mice, expres sing the IL-1 beta gene fused to a heterologous signal sequence under the c ontrol of the mouse immunoglobulin enhancer (E mu) A prominent hyperplasia and a disturbed microarchitecture of lymphoid tissues were observed in the transgenic mice. The CD4(+) T cells in the hyperplastic lymphoid organs see med to invade the majority of the lymphoid organs including B-cell restrict ed areas. Analysis of lymph node cells revealed an increased frequency of C D4(+) CD44(high) CD62L(-) T cells and local secretion of IL-2 and IL-4, com patible with an elevated number of activated T cells. Furthermore, signific ant levels of human IL-1 beta in sera and high concentrations of serum immu noglobulin G (IgG) were observed in the transgenic mice. The data suggest a role for IL-1 beta in controlling lymphoid microarchitecture and, when ove r-expressed, breaking the threshold in T-helper-B-cell interaction.