Cutting edge: B7/CD28 interactions regulate cell cycle progression independent of the strength of TCR signaling

The role of B7/CD28 signals in Ag-induced cell cycle progression of CD4⁺ T cells was examined using the technique of CFSE dye dilution and flow cytometry. In wild-type T cells, proliferation was directly related to the concentration of Ag available to the APC. Consistent with this, the rate of G₀→G₁ cell cycle progression varied with the concentration of Ag. However, cell division by T cell blasts occurred at a constant rate, independent of Ag concentration. G₀→G₁ phase progression by CD28-deficient CD4⁺ T cells or wild-type T cells cultured in the presence of neutralizing anti-B7 mAbs was slowed, confirming that a synergy does exist between TCR and CD28 signaling in the initial activation of the T cells. However, unlike the TCR, the strength of CD28 stimulation was also shown to play a unique role in controlling the rate of cell division by T cell blasts.