The interleukin 7 receptor (IL-7R) plays a crucial role in early B-and T-cell development. It consists of a unique a chain and a common y chain [IL-2 receptor y chain (IL-2Ry)]. Gene inactivation of IL-7, IL-7R, and IL-2Ry resulted in severe impairment of B and T lymphopoiesis in mice. In addition, IL-2Ry-deficient mice lack yS T cells in the skin and have the impaired development of natural killer (NK) cells and intraepithelial lymphocytes. To explore the role of IL-7/IL-7R system in yS T-and NK-cell development, we have generated and analyzed IL-7R-deficient mice. y6 T cells were absent from skin, gut, liver, and spleen in the deficient mice. In contrast, c43 T and B cells were detected in reduced, but certain, numbers, and NK cells developed normally. The y6 T-cell development in fetal and adult thymus was also completely blocked. These results clearly demonstrate that the signal from IL-7R is indispensable for y6 T-cell development in both thymic and extrathymic pathways. On the contrary, it is suggested that NK-cell development requires cytokine(s) other than IL-7.Interleukin 7 (IL-7) is a growth factor for early B-and T-cell precursors. It was first characterized by its ability to support the growth of B-cell precursors. Subsequently, it has been shown to support survival and growth of early thymocytes and promote rearrangement of T-cell receptor (TCR) ,B and -y chains in fetal thymus and fetal liver cultures (1, 2). In vivo administration of neutralizing antibodies to IL-7 and IL-7 receptor (IL-7R) resulted in the inhibition of both B and T lymphopoiesis (3, 4). IL-7R consists of two polypeptides: a unique a chain (IL-7Ra) and a common -y chain (IL-2R 'y chain, IL-2R-y) (5, 6). IL-7R shares the IL-2R-y with the receptors for IL-2, IL-4, IL-9, and IL-15 (7 and V-y4 but not of V-y3 or V-y5 genes and sustained expression of RAG-1 and RAG-2 genes (1, 2). Collectively, these results strongly suggest that IL-7 may be also involved in the development and the maintenance of 'y6 T cells in the thymus and the periphery. Gene inactivation studies have been carried out to elucidate the in vivo function of various cytokines and their receptors. In IL-2R-y-deficient mice, numbers of T, B, and natural killer (NK) cells are reduced (15,16). In addition, DETCs are absent from the skin and the development of IELs is severely diminished. In contrast, mice deficient for IL-2, IL-4, or both cytokines have normal numbers of mature T and B cells (17, 18). On the other hand, in both IL-7-and IL-7R-deficient mice, the numbers of lymphocytes are reduced (19,20), suggesting that the impairment of T and B lymphopoiesis in IL-2Ry-deficient mice is caused by depletion of the signal by IL-7. However, studies have not been reported on the development of y8 T and NK cells in IL-7R-deficient mice.To elucidate the role of IL-7/IL-7R system in y8 T-cell development, we have generated and analyzed IL-7R-deficient mice. yS T cells were absent from these mice, while decreased, but certain, numbers of mature af3 T cells were detected. ...

Platelet-activating factor (PAF) is a potent phospholipid mediator with diverse biological activities in addition to its well-known ability to stimulate platelet aggregation. Pharmacologic studies had suggested a role for PAF in pregnancy, neuronal cell migration, anaphylaxis, and endotoxic shock. Here we show that disruption of the PAF receptor gene in mice caused a marked reduction in systemic anaphylactic symptoms. Unexpectedly, however, the PAF receptor–deficient mice developed normally, were fertile, and remained sensitive to bacterial endotoxin. These mutant mice clearly show that PAF plays a dominant role in eliciting anaphylaxis, but that it is not essential for reproduction, brain development, or endotoxic shock.

We generated interleukin-5 receptor alpha chain (IL-5R alpha)-deficient (IL-5R alpha-/-) mice by gene targeting. The IL-5R alpha-/- mice showed decreased numbers of B-1 cells concomitant with low serum concentrations of IgM and IgG3. They showed no IL-5-induced enhancement of B cell responses to T-independent antigens. The number of alpha beta T cell receptor-positive thymocytes tended to decrease in 3-week-old IL-5R alpha-/- mice, returning to normal by 6 weeks of age. The IL-5R alpha-/- mice produced basal levels of eosinophils, while their bone marrow cells failed to form eosinophilic colonies in response to IL-5. Impaired eosinophilopoiesis in IL-5R alpha-/-mice enhanced the survival of Angiostrongylus cantonensis. These results indicate that IL-5-induced eosinophils serve as potent effector cells in the killing of Angiostrongylus cantonensis in mice.

IL-7R-deficient mice have severely impaired expansion of early lymphocytes and lack γδ T cells. To elucidate the role of IL-7R on γδ T cell development, we analyzed the rearrangements of TCR-α, β, γ, and δ genes in the thymus of the IL-7R-deficient mice. Southern blot analysis with a Jγ1 probe revealed that more than 70% of Jγ1 and Jγ2 alleles are recombined to form distinct Vγ1.2–Jγ2 and Vγ2–Jγ1 fragments in control mice. On the contrary, no such recombination was detected in the mutant mice. The rearrangements in the TCR-α, β, and δ loci were comparably observed in control and mutant mice. PCR analysis indicated that the V–J recombination of all the Vγ genes is severely hampered in the mutant mice. The mRNA of RAG-1, RAG-2, Ku-80, and terminal deoxynucleotidyl transferase (TdT) genes was equally detected between control and mutant thymi, suggesting that the expression of common recombination machinery is not affected. These data demonstrated that the V–J recombination of the TCR γ genes is specifically blocked in the IL-7R-deficient mice and suggested the presence of highly specific regulation for TCR γ gene rearrangement.