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 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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens / metabolism
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B7-1 Antigen / metabolism
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B7-1 Antigen / physiology*
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CD28 Antigens / genetics
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CD28 Antigens / metabolism
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CD28 Antigens / physiology*
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism*
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Cell Cycle / genetics
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Cell Cycle / immunology*
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Cell Division / genetics
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Cell Division / immunology
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Cells, Cultured
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G1 Phase / genetics
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G1 Phase / immunology
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Ovalbumin / immunology
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Ovalbumin / metabolism
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Receptors, Antigen, T-Cell / physiology*
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Resting Phase, Cell Cycle / genetics
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Resting Phase, Cell Cycle / immunology
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Signal Transduction / genetics
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Signal Transduction / immunology*
Substances
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Antigens
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B7-1 Antigen
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CD28 Antigens
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Receptors, Antigen, T-Cell
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Ovalbumin