Lymphohaematopoietic abnormalities and systemic lymphoproliferative disorder in interleukin-2 receptor γ chain-deficient mice

Interleukin-2 (IL-2) receptor γ chain-deficient mice with a truncated mutation showed the absence or severe reduction of natural killer cells, decreased numbers of T- and B-cells, marked hypoplasia of the thymus and peripheral lymphoid tissues, defective formation of lymphoid follicles and germinal centre in the peripheral lymphoid tissues, and the absence of Payer's patches in the intestinal mucosa. In addition, marked splenomegaly with extramedullary haematopoiesis, increased level of IgM and decreased levels of IgG and IgE in serum, severe reduction of conventional B cells (B- 2) in the peripheral lymphoid tissues, the presence of IgM-producing CD5⁺ B cells (B-1) and their differentiation into plasma cells and Motto cells in the spleen, and increased production and differentiation of macrophages in various tissues were found in the mutant mice. However, the development of both marginal metallophilic macrophage populations in the spleen and of their related macrophages in the other tissues of the mutant mice was severely impaired. All these abnormalities seem to be induced by the loss-of-function of the IL-2 receptor γ chain. From 8 weeks of age on, inflammatory changes occurred in the intestines, mesenteric lymph nodes, lungs, liver, and kidneys of the mutant mice. Besides the absence of Hassall's corpuscles, thymic cysts were frequently observed in the mutant mice. These pathological abnormalities suggest that the γ chain is implicated not only in lymphoid and haematepoietic development but also in thymic epithelial cell ontogeny.