Glucocorticoids regulate TCR-induced elevation of CD4: functional implications.
CD4 serves as a coreceptor during Ag recognition by the TCR. This interaction results in a marked increase in the sensitivity of a T cell to Ag presented by MHC class II molecules. Here we report that activation of T cells either by plate-bound mAb (anti-TCR, anti-CD3) or soluble activators (staphylococcal enterotoxin A, Con A) is associated with an (up to 3-fold) increase in CD4 cell surface expression on CD25+ cells, which was maximal after 72-96 h. Incubation with the glucocorticoid hormone corticosterone (CORT) shifted the enhancement of CD4 expression to a point about 24 h earlier than that observed in control cultures. In parallel, the proliferative response of these CORT-treated cells was profoundly enhanced. An involvement of increased CD4 expression in this enhanced proliferative response was evidenced by the observation that T cell proliferation in CORT-treated cultures was much less sensitive to inhibition by an inhibitory, nondepleting anti-CD4 mAb than that in control cultures. TCR down-regulation was, however, not affected by CORT. Thus, based on this study and previous reports we propose that both TCR-mediated signals and glucocorticoids are important physiological regulators of CD4 expression. In addition, these findings may be of significance for the sensitivity of CD4+ cells to HIV infection upon T cell activation, as the efficacy of primary patient HIV entry depends on the level of surface CD4.
Wiegers
G J
GJ
Section of Neuroimmunoendocrinology, Max Planck Institute of Psychiatry, Munich, Germany.
Stec
I E
IE
Klinkert
W E
WE
Reul
J M
JM
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003345:Corticosterone