Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence.
The costimulatory molecule CD28 has a restricted tissue distribution and is expressed on T cells and some plasmacytoma cells. Although CD28 is constitutively expressed, its expression is transiently down-regulated following T cell activation and declines progressively with in vitro senescence. In vivo, CD8+ T cells and, less frequently, CD4+ T cells may completely lose CD28 surface expression during chronic infections and with aging. This correlates with changes of nuclear protein-binding activities to two motifs, site alpha and beta, within the CD28 minimal promoter. Both alpha- and beta-bound complexes are found only in lymphoid tissues, in CD28+ T cells, and in some transformed B cells. These complexes are coordinately expressed except during replicative senescence, which is characterized by the down-modulation of site beta- but not site alpha-binding activities. In contrast, T cell activation induces a parallel decline in both site alpha- and beta-binding activities. CD4+ and CD8+ T cells differ in their beta-binding profiles, which may explain the more pronounced down-regulation of CD28 in senescent CD8+ T cells. In vivo expanded CD4+CD28null and CD8+CD28null T cells uniformly lack alpha- and beta-bound complexes, resembling the pattern seen in chronically activated cells and not of senescent cells.
Vallejo
A N
AN
Division of Rheumatology, Department of Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA. vallejo.abbe@mayo.edu
Brandes
J C
JC
Weyand
C M
CM
Goronzy
J J
JJ
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001483:Base Sequence; D018106:CD28 Antigens / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D016922:Cellular Senescence / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D014157:Transcription Factors