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Differential regulation of fibronectin receptor subunit gene and cell surface expression in human peripheral blood T lymphocytes

Differential regulation of fibronectin receptor subunit gene and cell surface expression in human peripheral blood T lymphocytes

Journal of Immunology 146(5): 1484-1489

ISSN/ISBN: 0022-1767

PMID: 1825219

Members of the .beta.1 subfamily of heterodimeric integrins, such as the fibronectin receptors .alpha.5.beta.1 and .alpha.4.beta.1, are expressed on human T lymphocytes. The presence of these two adhesion receptors on T lymphocytes suggests an involvement in cell-cell and cell-extracellular matrix interactions that may be important for the development of immune and inflammatory reactions. We have examined the cell surface expression of .alpha.5, .alpha.4, and .beta.1 subunits on purified peripheral blood T lymphocytes before and after activation with Con A and PMA. Freshly isolated T lymphocytes contained distinct fractions expressing high or low levels of .alpha.5 and .beta.1. Only a high expressing T lymphocyte population was present after 72-h culture with Con A and PMA. Time course analysis indicated that the shift in .alpha.5 and .beta.1 expression occurred during the first 24 h after addition of activating agents and occurred in the absence of proliferation. In contrast to .alpha.5 and .beta.1, essentially all freshly isolated T lymphocytes expressed high levels of .alpha.4. After 72-h culture with Con A and PMA, a wide distribution of .alpha.4 expression was observed. Further experiments showed that after activation, a proportion of CD4-positive cells decreased their surface expression of .alpha.4, but increased their surface expression of .alpha.5 and .beta.1. In contrast, most CD8-positive cells increased their surface expression of .alpha.5, .beta.1, and .alpha.4 upon activation. An examination of mRNA levels in pan-T lymphocyte cultures after activation indicated that .alpha.5 and .alpha.4 mRNA expression decreased, whereas .beta., mRNA expression was unchanged, in Con A/PMA-activated cells as compared to those cultured in medium alone. Our results indicate that T lymphocyte activating agents may differentially affect the expression of .alpha.5.beta.1 and .alpha.4.beta.1, thus providing a mechanism for the selective regulation of binding interactions that occur at sites of immune reactions.

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