LYMPHOPENIA IN INTERLEUKIN (IL)-7 GENE-DELETED MICE IDENTIFIES IL-7 AS A NONREDUNDANT CYTOKINE

Interleukin (IL)-7 is a potent stimulus for immature T and B cells and , to a lesser extent, mature T cells. We have inactivated the IL-7 gen e in the mouse germline by using gene-targeting techniques to further understand the biology of IL-7. Mutant mice were highly lymphopenic in the peripheral blood and lymphoid organs. Bone marrow B lymphopoiesis was blocked at the transition from pro-B to pre-B cells. Thymic cellu larity was reduced 20-fold, but retained normal distribution of CD4 an d CD8. Splenic T cellularity was reduced 10-fold. Splenic B cells, als o reduced in number, showed an abnormal population of immature B cells in adult animals. The remaining splenic populations of lymphocytes sh owed normal responsiveness to mitogenic stimuli. These data show that proper T and B cell development is dependent on IL-7. The IL-7-deficie nt mice are the first example of single cytokine-deficient mice that e xhibit severe lymphoid abnormalities.