The Journal of Immunology, Vol 146, Issue 5 1484-1489, Copyright © 1991 by American Association of Immunologists

ARTICLES

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

FR Kohn, ME Grigg and HG Klingemann
Terry Fox Laboratory for Hematology/Oncology, British Columbia Cancer Agency, Vancouver, Canada.

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 1 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.