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FASEB J. 2008 May;22(5):1426-39. doi: 10.1096/fj.07-9264com. Epub 2008 Jan 2.

Alpha-dystroglycan is involved in positive selection of thymocytes by participating in immunological synapse formation.

Author information

1
Department of Immunology, Shanghai Medical College of Fudan University, 138 Yixueyuan Rd., Shanghai 200032, China.

Abstract

Alpha-dystroglycan has been proved to be involved in lymphocyte activation by participating in immunological synapse (IS) formation. Considering the existence of IS formation in thymic development, we questioned whether alpha-dystroglycan was expressed in thymus and influenced thymic development. In this study, we demonstrated that alpha-dystroglycan was expressed on fetal thymocytes, especially on double-positive (DP, CD4(+)CD8(+)) cells. Blocking alpha-dystroglycan by treatment of fetal thymus organ culture (FTOC) with anti-alpha-dystroglycan antibody IIH6C4 decreased the number of DP cells compared with nontreated or isotype antibody controls. Down-regulation of alpha-dystroglycan by retroviruses carrying antisense cDNA of dystroglycan in reaggregate thymus organ culture (RTOC) further confirmed these results. Enhanced apoptosis of DP cells was observed after blocking alpha-dystroglycan. Interestingly, we found that blocking alpha-dystroglycan reduced IS formation between DP cells and thymic epithelial cells. Furthermore, blocking alpha-dystroglycan up-regulated CD95/CD95L expression and reduced Bcl-2 expression on DP cells in the developing thymus. Finally, the increase in the apoptosis of DP cells was associated with a consequent decrease in the positive selection, as indicated by the reduction of both ERK phosphorylation in DP cells and single-positive (SP, CD4(+) or CD8(+)) cell outcome. Altogether, these results indicated that alpha-dystroglycan was involved in positive selection of thymocytes by participating in the IS formation.

PMID:
18171694
DOI:
10.1096/fj.07-9264com
[Indexed for MEDLINE]

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