CD28 costimulation is required not only to induce IL-12 receptor but also to render Janus kinases/STAT4 responsive to IL-12 stimulation in TCR-triggered T cells
Wr. Park et al., CD28 costimulation is required not only to induce IL-12 receptor but also to render Janus kinases/STAT4 responsive to IL-12 stimulation in TCR-triggered T cells, EUR J IMMUN, 31(5), 2001, pp. 1456-1464
The activation of resting T cells for the acquisition of various functions
depends on whether CD28 costimulatory signals are provided upon T cell rece
ptor stimulation. Here, we investigated how CD28 costimulation functions to
allow TCR-triggered resting T cells to acquire 1L-12 responsiveness. When
T cells are stimulated with low doses of anti-CDS mAb, CD28 costimulation w
as required for the optimal levels of IL-12 receptor (IL-12R) expression. H
owever, stimulation of T cells with high doses of anti-CDS alone induced co
mparable levels of IL-12R expression to those induced upon CD28 costimulati
on. Nevertheless, there was a substantial difference in IL-12 responsivenes
s between these two groups of T cells: compared to anti-CD28-costimulated T
cells, T cells that were not costimulated with anti-CD28 exhibited decreas
ed levels of Janus kinases (JAK) JAK2/TYK2 and STAT4 phosphorylation and IF
N-gamma production following IL-12 stimulation. importantly, STAT6 phosphor
ylation following IL-4 stimulation was not decreased in anti-CD28-uncostimu
lated T cells. These resutls indicate that CD28 costimulation not only cont
ributes to up-regulating IL-12R expression but is also required to render J
AKs/STAT4 responsive to IL-12 stimulation.