Laminin 5 in the Human Thymus: Control of T Cell Proliferation via α(6)β(4) Integrins

Laminin 5 (α(3)β(3)γ(2)) distribution in the human thymus was investigated by immunofluorescence on frozen sections with anti-α(3), -β(3), and -γ(2) mAbs. In addition to a linear staining of subcapsular basal laminae, the three mAbs give a disperse staining in the parenchyma restricted to the medullary area on a subset of stellate epithelial cells and vessel structures. We also found that laminin 5 may influence mature human thymocyte expansion; while bulk laminin and laminin 2, when cross-linked, are comitogenic with a TCR signal, cross-linked laminin 5 has no effect. By contrast, soluble laminin 5 inhibits thymocyte proliferation induced by a TCR signal. This is accompanied by a particular pattern of inhibition of early tyrosine kinases, including Zap 70 and p59(fyn) inhibition, but not overall inhibition of p56(lck). Using a mAb specific for α(6)β(4) integrins, we observed that while α(3)β(1) are known to be uniformly present on all thymocytes, α(6)β(4) expression parallels thymocyte maturation; thus a correspondence exists between laminin 5 in the thymic medulla and α(6)β(4) on mature thymocytes. Moreover, the soluble Ab against α(6)β(4) inhibits thymocyte proliferation and reproduces the same pattern of tyrosine kinase phosphorylation suggesting that α(6)β(4) is involved in laminin 5–induced modulation of T cell activation.