Cutting Edge: B7/CD28 Interactions Regulate Cell Cycle Progression Independent of the Strength of TCR Signaling

Abstract

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.

Cytoplasmic Entry of Listeria monocytogenes Enhances Dendritic Cell Maturation and T Cell Differentiation and Function

“…The recruitment of T cells into cell cycle and the subsequent rate of division have been reported to be enhanced by costimulatory molecules such as B7.1 and B7.2 (29,38). Our data support these findings by demonstrating that in the absence of costimulatory molecules, in particular B7.1 and/or B7.2, both the percentage of T cells dividing and the number of cell divisions detected were reduced (Fig.…”

Costimulation via CD55 on Human CD4+ T Cells Mediated by CD97

“…Coengagement of CD28 and CD3 on T cells results in increased cell cycle progression compared with CD3 engagement alone, resulting in a higher number of cells leaving G 0 phase (24). Similar results were obtained with CD55/CD3 stimulation.…”

Proliferating CD4+ T Cells Undergo Immediate Growth Arrest upon Cessation of TCR Signaling In Vivo

“…Under such conditions, continued TCR ligation can, in fact, interfere with this autocrine proliferative pathway (12). Our own investigations of CD4 ϩ T cell proliferation have extended this work, but further indicate that sustained TCR and CD28 signaling can be both necessary and sufficient to maintain an optimal rate of cell division when access to IL-2 in the in vitro cultivation system is limited (13)(14)(15). IL-2 has not been observed to play a major role in Ag-dependent naive CD4 ϩ T cell clonal expansion in vivo (16).…”