M. Iwao et al., Interaction of merosin (laminin 2) with very late activation antigen-6 is necessary for the survival of CD4(+) CD8(+) immature thymocytes, IMMUNOLOGY, 99(4), 2000, pp. 481-488
The laminin alpha 2-chain is a component of merosin, a member of the lamini
n family molecules, which is mainly expressed in the basement membranes of
striated muscle. It is known that laminin alpha 2 gene (lama2) null mutant
mice (dy(3k)/dy(3k)) exhibit congenital muscular dystrophy (CMD). Because t
he laminin alpha 2-chain is also expressed in the thymus, the role of meros
in in the thymus was examined. In association with the onset of muscular dy
strophy, CD4(+) CD8(+) double-positive (DP) thymocytes disappear by apoptot
ic cell death, while CD4(+) CD8(-) or CD4(-) CD8(+) thymocytes remain. In o
rder 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 activ
ation antigen-6 (VLA-6), a candidate merosin ligand in the thymus, and mero
sin 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 thym
ic 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 sig
nal, and that survival is supported by the interaction between VLA-6 and me
rosin.