| First Author | Chastagner P | Year | 2002 |
| Journal | J Immunol | Volume | 169 |
| Issue | 7 | Pages | 3644-51 |
| PubMed ID | 12244156 | Mgi Jnum | J:79241 |
| Mgi Id | MGI:2387542 | Doi | 10.4049/jimmunol.169.7.3644 |
| Citation | Chastagner P, et al. (2002) Lymphoadenopathy in IL-2-Deficient Mice: Further Characterization and Overexpression of the Antiapoptotic Molecule Cellular FLIP. J Immunol 169(7):3644-51 |
| abstractText | 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. |
