Study of Tenascin-C on the thymocyte differentiation in mice

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Tenascin-C (TN-C), one of the biggest extracellular matrix proteins, is expressed at considerable levels in the thymuses and spleens of adult mice. In order to investigate the function of TN-C in the immune system, we subjected TN-C deficient C3H/HeN congenic mice to sublethal X-irradiation. In the first week after irradiation, we found lineage negative-CD44 dull positive-CD25 positive thymocytes of TN-C deficient mice disappeared one day earlier than those of wild type mice. This strongly suggests that TN-C suppresses the differentiation of X-ray low sensitive thymic T cells which are believed as the major source of thymus reconstitution. We analyzed thymuses of wild-type mice biochemically and immunohistochemically. The expression of TN-C elevated strongly within a week after irradiation, and its expression was observed primarily at intra medullary lymphocytes and cortical blood vessels.On the functional assay using mixed lymphocyte reaction (MLR) method, responder cells from TN-C deficient GRS/A showed significantly low response to the stimulator cells from wild-type BALB/c than those from TN-C deficient BALB/c. This finding brought us the two possibilities ; one is that TN-C suppressed MLR overall via some suppressive factors or signals, and another is that TN-C worked to decrease the development of MLR reactive specific T cell clones. In order to clarify the latter possibility, we analyzed the T cell receptor β chain (Vβ) expression of peripheral lymph node T cells from TN-C deficient and wild-type GRS/A mice. However, we could not find any difference between them. On the contrary, FACS analyses of memory/activated T cells from non-stimulated spleens and lymph nodes indicated that the existence of TN-C might modify the induction of peripheral memory T cells.