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Division of Rheumatology, Department of Medicine, Mayo Clinic and Foundation, Rochester, MN 55905
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 
and ß, within the CD28 minimal promoter. Both
- and ß-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 ß-
but not site -binding activities. In contrast, T cell activation
induces a parallel decline in both site - and ß-binding
activities. CD4+ and CD8+ T cells differ in
their ß-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 - and
ß-bound complexes, resembling the pattern seen in chronically
activated cells and not of senescent cells.
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