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Death-Defying Factor Identified Apoptotic

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Death-Defying Factor Identified Apoptotic HIGHLIGHTS HAEMATOPOIESIS controls, and a marked proportion of cells in the fetal liver, which was less than a third of the size of that in anamorsin-sufficient embryos, were Death-defying factor identified apoptotic. Interestingly, the absolute number of haematopoietic stem cells and immature pro- Shibayama et al. used an interleukin-3 (IL-3)- erthyrocytes was normal in the fetal liver of independent variant of a mouse IL-3-dependent anamorsin-deficient embryos, indicating that cell line to isolate molecules that conferred anamorsin probably has a role in the late stages of resistance to apoptosis induced by IL-3 star- haematopoiesis and terminal differentiation. vation. cDNA encoding anamorsin — a novel This was confirmed by the observation that protein with no homology to any known anamorsin-deficient fetal liver cells were severely anti-apoptotic molecule — was isolated from impaired in their ability to generate myeloid and cells that survived IL-3 deprivation. The anti- erythroid colonies when cultured in the presence apoptotic effect of this protein was confirmed of the appropriate cytokines. by the observation that stable expression of This study identifies anamorsin as a funda- anamorsin by the parental cell line and by a mental anti-apoptotic factor induced by second IL-3-dependent cell line conferred cytokines during haematopoiesis. Future studies Cytokines such as stem-cell factor (SCF) and resistance to apoptosis after IL-3 withdrawal. will focus on the mechanisms by which the anti- erythropoietin (EPO) have a crucial role in In addition to IL-3, anamorsin expression apoptotic effects of anamorsin are mediated, and haematopoiesis, inducing mitogenic and anti- was induced by other cytokines, including SCF initial studies by the authors indicating that apoptotic factors. Although the molecular and EPO, indicating that it probably has a general expression of Bcl-XL and Jak2 is downregulated pathways by which these cytokines mediate role in mediating the anti-apoptotic effects of in the absence of anamorsin should provide a their effects remain ill defined, a report in The cytokine exposure in vitro. good basis to initiate these investigations. Journal of Experimental Medicine has now The in vivo significance of this molecule was Karen Honey shed light on the signalling cascades involved, highlighted by the observation that anamorsin- References and links identifying anamorsin as a novel anti-apoptotic deficient mice die in late gestation. Anamorsin- ORIGINAL RESEARCH PAPER Shibayama, H. et al. Identification of a cytokine-induced antiapoptotic molecule factor induced by cytokines during definitive deficient embryos were anaemic, having half the anamorsin essential for definitive haematopoiesis. J. Exp. Med. haematopoiesis. number of peripheral red blood cells as littermate 199, 581–592 (2004) REPRODUCTIVE IMMUNOLOGY Pregnancy regulators How does the maternal immune system when mice were mated with syngeneic males, tolerate the persistence of paternal indicating that the presence of fetal alloantigens during pregnancy? A report in alloantigen is not required to drive expansion Nature Immunology addresses this question of the CD4+CD25+ T-cell pool. In vitro, these and describes the systemic expansion of cells could suppress the proliferation of maternal regulatory T-cell populations, alloreactive cells in a mixed lymphocyte which can suppress aggressive allogeneic reaction. Furthermore, when whole immune responses against the fetus. lymphocyte preparations or CD25+ cell- Several localized mechanisms have depleted preparations from pregnant mice previously been described that contribute to were adoptively transferred to nude female fetal evasion from immune attack, including mice that were subsequently mated, those expression of HLA-G and FAS ligand that received samples depleted of CD25+ cells (CD95L) by fetal tissues, which inhibits the did not sustain normal pregnancy. However, activation of natural killer (NK) cells and if the mice that received CD25+ cell-depleted induces apoptosis of activated maternal preparations were mated with a syngeneic lymphocytes, respectively. Nevertheless, male, pregnancy was normal, indicating maternal alloreactive lymphocytes can that the regulatory function of these T cells still be detected. is only required when the fetus expresses experiments hope to determine whether In this study, Betz and colleagues showed alloantigen, which is inevitable under non- these cells are important in preventing that the number of naturally occurring experimental circumstances. pregnancy failures in humans. regulatory T cells (CD4+CD25+) in the lymph The presence of these regulatory Lucy Bird nodes and spleen of pregnant mice was populations might explain the observed References and links markedly increased compared with non- remission of some autoimmune diseases ORIGINAL RESEARCH PAPER Aluvihare, V. R., Kallikourdis, M. & Betz, A. G. Regulatory T cells mediate pregnant control mice. This expansion of the and enhanced maternal tolerance to some maternal tolerance to the fetus. Nature Immunol. CD4+CD25+ T-cell population even occurred paternal grafts during pregnancy. Future 3, 266–271 (2004) 164 | MARCH 2004 | VOLUME 4 www.nature.com/reviews/immunol.
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