| First Author | Schneider E | Year | 2004 |
| Journal | J Immunol | Volume | 172 |
| Issue | 9 | Pages | 5262-8 |
| PubMed ID | 15100264 | Mgi Jnum | J:89642 |
| Mgi Id | MGI:3041007 | Doi | 10.4049/jimmunol.172.9.5262 |
| Citation | Schneider E, et al. (2004) Pro-Th1 cytokines promote Fas-dependent apoptosis of immature peripheral basophils. J Immunol 172(9):5262-8 |
| abstractText | We have previously characterized immature hemopoietic cells of the basophil lineage as a lin(-)c-kit(-) population, which responds to IL-3 by enhancing its histamine synthesis through histidine decarboxylase activation. Herein, we show both in vitro and in vivo that exposure to the pro-Th1 cytokines IL-12 and IL-18 promotes Fas-dependent apoptosis of these cells in the spleen. This conclusion was supported by the following findings: 1) A 24-h treatment with IL-12 plus IL-18 enhanced Fas expression and annexin staining among basophil precursor-enriched lin(-)c-kit(-) splenocytes. 2) Fas or Fas ligand deficiency in mutant mice abolished the inhibitory effect of IL-12 plus IL-18 on IL-3-induced histamine production. 3) The large spectrum inhibitor of the caspase cascade, benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone, significantly reduced the effect of IL-12 plus IL-18. The inhibition of histamine production was mediated through NK cells, since it failed to occur upon stimulation of spleen cells from NK cell-deficient mice or after NK cell depletion. IL-12 plus IL-18 rendered NK cells cytotoxic against Fas-transfected target cells and promoted their production of IFN-gamma and TNF-alpha, which are both essential for sensitizing histamine-producing cells to the Fas death pathway. This is the first evidence that pro-Th1 cytokines can promote apoptosis of immature peripheral histamine-producing cells, thus limiting Th2 immune responses. Comparable in vivo data as well as increased histamine production in the spleen of aged Fas-deficient lpr mice support its physiological relevance. |
