Lymphoadenopathy in IL-2-deficient mice: Further characterization and overexpression of the antiapoptotic molecule cellular FLIP

Patricia Chastagner, Jay Reddy, Jacques Thèze

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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.

Original languageEnglish (US)
Pages (from-to)3644-3651
Number of pages8
JournalJournal of Immunology
Volume169
Issue number7
DOIs
StatePublished - Oct 1 2002

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CASP8 and FADD-Like Apoptosis Regulating Protein
Interleukin-2
Lymph Nodes
Lymphocytes
Spleen

ASJC Scopus subject areas

  • Immunology

Cite this

Lymphoadenopathy in IL-2-deficient mice : Further characterization and overexpression of the antiapoptotic molecule cellular FLIP. / Chastagner, Patricia; Reddy, Jay; Thèze, Jacques.

In: Journal of Immunology, Vol. 169, No. 7, 01.10.2002, p. 3644-3651.

Research output: Contribution to journalArticle

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