Modulation of fibronectin and thymic stromal cell-dependent thymocyte maturation by retinoic acid

Daniela Meco, Susanna Scarpa, Maddalena Napolitano, Marella Maroder, Diana Bellavia, Ruggero De Maria, Maria Ragano-Caracciolo, Luigi Frati, Andrea Modesti, Alberto Gulino, Isabella Screpanti

Research output: Contribution to journalArticle

Abstract

Retinoic acid (RA) controls the differentiation of a variety of cell types, although its role in influencing T cell development and the mechanisms potentially involved have not been thoroughly investigated. To study the ability of RA to modulate T cell development, we established a thymic stromal cell line (TC-1S) that supports the phenotypic maturation of CD4-8- double negative (DN) or CD3-4-8- triple negative (TN) thymocyte precursors. Cocultures of either DN or TN thymocytes on a monolayer of TC-1S cells resulted in the appearance of thymocytes with a more mature phenotype (CD4+8+ double positive, CD4+ or CD8+ single positive, and CD3(low) cells). Double negative T cell contact with TC-1S cells also increased the production of fibronectin (FN) by the thymic stroma and the expression of the VLA-4 FN receptor on the DN cells. Ab-mediated inhibition of the interaction between FN and its receptors significantly reduced the level of induced T cell maturation. Addition of RA either to TC-1S cells alone or to the coculture with DN cells decreased stromal cell FN expression, antagonized DN cell-induced increase in stromal cell FN production and significantly inhibited in vitro thymocyte maturation. The effects of RA were likely mediated by RA acid receptors α and γ expressed both in DN thymocytes and TC-1S cells. Together these data suggest that FN/VLA-4 interaction may be an important component of stromal cell-dependent thymocyte phenotypic differentiation and that this interaction can be one of the targets for the influence of RA in T cell development.

Original languageEnglish
Pages (from-to)73-83
Number of pages11
JournalJournal of Immunology
Volume153
Issue number1
Publication statusPublished - Jul 1 1994

ASJC Scopus subject areas

  • Immunology

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