J. Cell Biol., Volume 144, Number 3, February 8, 1999 563-574

Laminin 5 in the Human Thymus: Control of T Cell Proliferation via ₆₄ Integrins

Mylène Vivinus-Nebot,^* Michel Ticchioni,^* Florence Mary,^* Paul Hofman,^§ Vito Quaranta, Patricia Rousselle,^¶ and Alain Bernard^*

^* Institut National de la Santé et de la Recherche Médicale, U343, Nice 06202, France;  Laboratoire Central d'Immunologie, Centre Hospitalier Universitaire, Nice 06202, France; ^§ Laboratoire d'Anatomie Pathologique, Centre Hospitalier Universitaire, Nice 06002, France;  Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037; and ^¶ Centre National de la Recherche Scientifique, UPR 412, Lyon 69367, France

Laminin 5 (₃₃₂) distribution in the human thymus was investigated by immunofluorescence on frozen sections with anti-₃, -₃, and -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 ₆₄ integrins, we observed that while ₃₁ are known to be uniformly present on all thymocytes, ₆₄ expression parallels thymocyte maturation; thus a correspondence exists between laminin 5 in the thymic medulla and ₆₄ on mature thymocytes. Moreover, the soluble Ab against ₆₄ inhibits thymocyte proliferation and reproduces the same pattern of tyrosine kinase phosphorylation suggesting that ₆₄ is involved in laminin 5-induced modulation of T cell activation.

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