Laminin 5 in the Human Thymus: Control of T Cell Proliferation via α₆β₄ Integrins

Laminin 5 (α₃β₃γ₂) distribution in the human thymus was investigated by immunofluorescence on frozen sections with anti-α₃, -β₃, and -γ₂ 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 α₆β₄ integrins, we observed that while α₃β₁ are known to be uniformly present on all thymocytes, α₆β₄ expression parallels thymocyte maturation; thus a correspondence exists between laminin 5 in the thymic medulla and α₆β₄ on mature thymocytes. Moreover, the soluble Ab against α₆β₄ inhibits thymocyte proliferation and reproduces the same pattern of tyrosine kinase phosphorylation suggesting that α₆β₄ is involved in laminin 5–induced modulation of T cell activation.