LYMPHOHAEMATOPOIETIC ABNORMALITIES AND SYSTEMIC LYMPHOPROLIFERATIVE DISORDER IN INTERLEUKIN-2 RECEPTOR-GAMMA CHAIN-DEFICIENT MICE

Interleukin-2 (IL-2) receptor gamma chain-deficient mice with a trunca ted mutation showed the absence or severe reduction of natural killer cells, decreased numbers of T- and B-cells, marked hypoplasia of the t hymus and peripheral lymphoid tissues, defective formation of lymphoid follicles and germinal centre in the peripheral lymphoid tissues, and the absence of Peyer's patches in the intestinal mucosa. In addition, marked splenomegaly with extramedullary haematopoiesis, increased lev el of IgM and decreased levels of IgG and IgE in serum, severe reducti on of conventional B cells (B-2) in the peripheral lymphoid tissues, t he presence of lgM-producing CD5(+) B cells (B-1) and their differenti ation into plasma cells and Motto cells in the spleen, and increased p roduction and differentiation of macrophages in various tissues were f ound in the mutant mice, However, the development of both marginal met allophilic macrophage populations in the spleen and of their related m acrophages in the other tissues of the mutant mice was severely impair ed. All these abnormalities seem to be induced by the loss-of-function of the IL-2 receptor gamma chain, From 8 weeks of age on, inflammator y changes occurred in the intestines, mesenteric lymph nodes, lungs, l iver, 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 gamma chain is impl icated not only in lymphoid and haematopoietic development but also in thymic epithelial cell ontogeny.