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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jul 1;88(13):5685–5689. doi: 10.1073/pnas.88.13.5685

Adhesion of immature thymocytes to thymic stromal cells through fibronectin molecules and its significance for the induction of thymocyte differentiation.

K Utsumi 1, M Sawada 1, S Narumiya 1, J Nagamine 1, T Sakata 1, S Iwagami 1, Y Kita 1, H Teraoka 1, H Hirano 1, M Ogata 1, et al.
PMCID: PMC51942  PMID: 1829526

Abstract

Only 10-15% of unseparated thymocytes adhered to culture plates precoated with fibronectin (FN), but 60-70% of the CD4-8- (double-negative) thymocyte population did. This population bound to FN but not to collagen, laminin, or vitronectin. Its binding to FN was inhibited by anti-FN antibody or a mixture of synthetic peptides corresponding to two different sites of FN, termed the V10 sequence and the RGDS (Arg-Gly-Asp-Ser) sequence, which interact, respectively, with the VLA-4 and VLA-5 FN receptors expressed on T-lineage cells. CD4-8- thymocytes also adhered to a monolayer of a thymic stromal cell clone, MRL104.8a, that induces growth-maintenance and differentiation of such thymocytes. The involvement of FN-FN receptor interaction in this adhesion was demonstrated by the following lines of evidence: (i) the MRL104.8a cells expressed FN molecules on their surface and (ii) the adhesion of CD4-8- thymocytes to MRL104.8a monolayers was almost completely inhibited by simultaneous addition of anti-FN antibody and a mixture of peptides (V10 plus RGDS) capable of binding to anti-FN receptors (VLA-4 and -5). Most important, blocking the adhesion of CD4-8- thymocytes to the thymic stromal cell monolayer resulted in potent inhibition of the differentiation of these thymocytes, which was otherwise induced toward the expression of CD4 and/or CD8 molecules. These results indicate that immature CD4-8- thymocytes adhere to thymic stromal cells preferentially through FN-FN receptor interaction and that such adhesion has a critical role in inducing and/or supporting the differentiation of these thymocytes.

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Selected References

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