| First Author | Do Y | Year | 2003 |
| Journal | Int Immunol | Volume | 15 |
| Issue | 11 | Pages | 1327-40 |
| PubMed ID | 14565931 | Mgi Jnum | J:86310 |
| Mgi Id | MGI:2679392 | Doi | 10.1093/intimm/dxg132 |
| Citation | Do Y, et al. (2003) Combined deficiency in CD44 and Fas leads to exacerbation of lymphoproliferative and autoimmune disease. Int Immunol 15(11):1327-40 |
| abstractText | Patients with mutations in Fas develop autoimmune lymphoproliferative disease (ALPS), while their family members with similar mutations are often normal, thereby suggesting that additional factors may play a role in the development of ALPS. In the current study, we tested the role of CD44 in the development of lymphoproliferative disease by generating CD44(-/-)/Fas(-/-) mice, which failed to express CD44 and Fas, and compared them to CD44(+/+)/Fas(-/-) mice that expressed CD44, but not Fas. The results showed that CD44(-/-)/Fas(-/-) mice developed a more severe lymphoproliferative and autoimmune disease when compared to CD44(+/+)/Fas(-/-) mice. This was indicated by increased numbers of cells in their lymph nodes, and a greater proportion of B220(+)CD4(-)CD8(-) (double-negative) T cells as well as antibodies against single-stranded DNA and chromatin. The heightened severity of lymphoproliferative disease seen in CD44(-/-)/Fas(-/-) mice correlated with increased resistance of T cells, but not B cells, to undergo activation-induced cell death (AICD). The current study suggests that deficiency in CD44 in combination with a defect in one of the molecules involved in the death receptor family such as Fas can further down-regulate AICD, and exacerbate the lymphoproliferative and autoimmune disease. |
