Differential regulation of fibronectin receptor subunit gene and cell surface expression in human peripheral blood T lymphocytes.
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.
Kohn
F R
FR
Terry Fox Laboratory for Hematology/Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Grigg
M E
ME
Klingemann
H G
HG
D003208:Concanavalin A / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics*; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005353:Fibronectins; D016023:Integrins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D003208:Concanavalin A; D013755:Tetradecanoylphorbol Acetate