Interaction of merosin (laminin 2) with very late activation antigen-6 is necessary for the survival of CD4+ CD8+ immature thymocytes.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Interaction of merosin (laminin 2) with very late activation antigen-6 is necessary for the survival of CD4+ CD8+ immature thymocytes.

Immunology. 2000 Apr;99(4):481-8. Unique Identifier : AIDSLINE MED/20253142
Iwao M; Fukada S; Harada T; Tsujikawa K; Yagita H; Hiramine C; Miyagoe Y; Takeda S; Yamamoto H; Department of Immunology, Graduate School of Pharmaceutical; Sciences, Osaka University, Suita, Osaka, Japan.

Abstract: The laminin alpha2-chain is a component of merosin, a member of the laminin family molecules, which is mainly expressed in the basement membranes of striated muscle. It is known that laminin alpha2 gene (lama2) null mutant mice (dy3k/dy3k) exhibit congenital muscular dystrophy (CMD). Because the laminin alpha2-chain is also expressed in the thymus, the role of merosin in the thymus was examined. In association with the onset of muscular dystrophy, CD4+ CD8+ double-positive (DP) thymocytes disappear by apoptotic cell death, while CD4+ CD8- or CD4- CD8+ thymocytes remain. In order to study the mechanisms leading to the selective death of DP cells in the absence of merosin, the role of the interaction between very late activation antigen-6 (VLA-6), a candidate merosin ligand in the thymus, and merosin was examined. The in vitro survival of thymocytes from normal mice was maintained by the addition of either anti-VLA-6 monoclonal antibodies (mAbs) or merosin. Furthermore, when the normal thymocytes were cultured on thymic epithelial cell lines, viable DP cell recoveries on wild-type epithelial cells were better than on cells from null mutant mice. The results suggest that DP cells are more sensitive to an uncharacterized apoptotic death signal, and that survival is supported by the interaction between VLA-6 and merosin.

Keywords: JOURNAL ARTICLE Animal Antibodies, Monoclonal/PHARMACOLOGY Apoptosis/DRUG EFFECTS Cell Survival/DRUG EFFECTS Cells, Cultured CD4-Positive T-Lymphocytes/METABOLISM/PATHOLOGY CD8-Positive T-Lymphocytes/METABOLISM/PATHOLOGY Epithelium/METABOLISM Gene Deletion Integrins/IMMUNOLOGY/*METABOLISM Laminin/ANALYSIS/GENETICS/*PHARMACOLOGY Mice Mice, Inbred BALB C Mice, Mutant Strains Muscular Dystrophy, Animal/*IMMUNOLOGY Support, Non-U.S. Gov't T-Lymphocytes/*METABOLISM/PATHOLOGY Thymus Gland/CHEMISTRY/IMMUNOLOGY

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A0080973

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