title: Lymphoadenopathy in IL-2-deficient mice: further characterization and overexpression of the antiapoptotic molecule cellular FLIP.
abstract: IL-2 was originally identified as a potent T cell growth factor. It was subsequently demonstrated that IL-2 also exerts proapoptotic effects under certain conditions. Inactivation of IL-2 by gene targeting in mice showed that whereas IL-2 is not essential for the generation, clonal expansion, or differentiation of lymphocytes to effector cells, it has a unique role in preventing the accumulation of activated lymphocytes. IL-2(-/-) mice show lymphoadenopathy and autoimmune reactions, suggesting that the proapoptotic effects of IL-2 may predominate in vivo. In this study, we confirm that lymph nodes (LNs) are enlarged in IL-2(-/-) animals, but surprisingly, we found that their spleens are almost normal in size. Subsequent to this observation, we compare lymphocytes from LNs and spleens of IL-2(-/-) and IL-2(+/-) animals to analyze molecular and cellular correlates of the immunopathological disorders found in IL-2-deficient mice. LN lymphocytes from IL-2(-/-) are selectively activated and show an enhanced survival capacity and an increased ability to proliferate in vitro when compared with LN cells from IL-2(+/-) mice and splenocytes from IL-2(-/-) and IL-2(+/-) mice. Because the apoptosis inhibitor FLIP has been shown in vitro to participate in the IL-2 control of activation-induced cell death, we analyze its expression in IL-2(-/-) mice. FLIP was found to be selectively overexpressed in the LNs of IL-2(-/-) mice, but no overexpression was found in spleen cells or thymocytes. These results suggest that FLIP, in conjunction with other IL-2-regulated genes previously characterized in our laboratory, is involved in controlling lymphoadenopathy in IL-2(-/-) mice.
authors.affiliation: Unité d'Immunogénétique Cellulaire, Département de Médecine Moléculaire, Institut Pasteur, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Chastagner
authors.forename: Jay
authors.initials: J
authors.lastname: Reddy
authors.forename: Jacques
authors.initials: J
authors.lastname: Thèze
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D007376:Interleukin-2 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008206:Lymphatic Diseases / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins; C506387:Cflar protein, mouse; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger