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 G(0)-->G(1) 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. G(0)-->G(1) 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.
Bonnevier
Jody L
JL
Rheumatic Division and Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA.
Mueller
Daniel L
DL
D000818:Animals; D000941:Antigens / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism / Q000502:physiology*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016193:G1 Phase / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
D000941:Antigens; D018122:B7-1 Antigen; D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin