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 gene 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 cellularity was reduced 20-fold, but retained normal distribution of CD4 and CD8. Splenic T cellularity was reduced 10-fold. Splenic B cells, also reduced in number, showed an abnormal population of immature B cells in adult animals. The remaining splenic populations of lymphocytes showed normal responsiveness to mitogenic stimuli. These data show that proper T and B cell development is dependent on IL-7. The IL-7-deficient mice are the first example of single cytokine-deficient mice that exhibit severe lymphoid abnormalities.
von Freeden-Jeffry
U
U
Department of Immunology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USA.
Vieira
P
P
Lucian
L A
LA
McNeil
T
T
Burdach
S E
SE
Murray
R
R
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D003208:Concanavalin A / Q000494:pharmacology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008221:Lymphoid Tissue / Q000473:pathology*; D008231:Lymphopenia / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
D007376:Interleukin-2; D015851:Interleukin-7; D011994:Recombinant Proteins; D003208:Concanavalin A