Lymphoid hyperplasia in transgenic mice over-expressing a secreted form of the human interleukin-1β gene product

To evaluate the biological effects of over-expression of interleukin- 1β (IL-1β) on the immune system we have generated transgenic mice, expressing the IL-1β gene fused to a heterologous signal sequence under the control of the mouse immunoglobulin enhancer (Eμ). 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 seemed to invade the majority of the lymphoid organs including B-cell restricted areas. Analysis of lymph node cells revealed an increased frequency of CD4⁺ CD44(high) CD62L^- T cells and local secretion of IL-2 and IL-4, compatible with an elevated number of activated T cells. Furthermore, significant levels of human IL-1β in sera and high concentrations of serum immunoglobulin G (IgG) were observed in the transgenic mice. The data suggest a role for IL- 1β in controlling lymphoid microarchitecture and, when over-expressed, breaking the threshold in T-helper-B-cell interaction.