Laminin 5 in the human thymus: Control of T cell proliferation via alpha(6)beta(4) integrins

Laminin 5 (alpha(3)beta(3)gamma(2)) distribution in the human thymus was in vestigated by immunofluorescence on frozen sections with anti-alpha(3), -be ta(3), and -gamma(2) mAbs. In addition to a linear staining of subcapsular basal laminae, the three mAbs give a disperse staining in the parenchyma re stricted 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 ea rly tyrosine kinases, including Zap 70 and p59(fyn) inhibition, but not ove rall inhibition of p56(lck). Using a mAb specific for alpha(6)beta(4) integ rins, we observed that while alpha(3)beta(1) are known to be uniformly pres ent on all thymocytes, alpha(6)beta(4), expression parallels thymocyte matu ration; thus a correspondence exists between laminin 5 in the thymic medull a and alpha(6)beta(4) On mature thymocytes. Moreover, the soluble Ab agains t alpha(6)beta(4) inhibits thymocyte proliferation and reproduces the same pattern of tyrosine kinase phosphorylation suggesting that alpha(6)beta(4) is involved in laminin 5-induced modulation of T cell activation.