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CD28 engagement by B7/BB-1 induces transient down-regulation of CD28 synthesis and prolonged unresponsiveness to CD28 signaling.

P S Linsley, J Bradshaw, M Urnes, L Grosmaire and J A Ledbetter
J Immunol April 15, 1993, 150 (8) 3161-3169;
P S Linsley
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J Bradshaw
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M Urnes
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L Grosmaire
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J A Ledbetter
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Abstract

Costimulatory molecules on the APC regulate T cell growth by providing signals that regulate responses to TCR occupancy. One such molecule is B7/BB-1, which triggers a T cell activation pathway by binding the CD28 and/or CTLA-4 cell-surface molecules. Expression and signaling activity of CD28 have been shown to increase after T cell activation by various polyclonal activators. Here we show that CD28 expression and signaling activity in activated T cells decrease after ligand binding to CD28. Stimulation of CD28 on PHA- or PMA-activated T cells by cross-linked mAb 9.3 or by co-culture with B7+ Chinese hamster ovary (CHO) cells caused a marked reduction of CD28 mRNA levels within 4 h. The decrease in CD28 mRNA was transient, and by 24 h of CD28 stimulation, CD28 mRNA was found at approximately initial levels. In contrast, CTLA-4 mRNA levels were usually up-regulated by CD28 triggering. Cell-surface expression of CD28, but not CD2 or CD3, decreased by 12 to 24 h after addition of B7+ CHO cells, but returned to initial levels or higher by 48 h. The ability of CD28 cross-linking on PMA-activated CD4+ cells to trigger calcium mobilization was also reduced by treatment with B7+ CHO cells, and remained reduced even after cell-surface expression of CD28 returned to normal levels. Thus, engagement of the CD28 receptor by its natural ligand B7/BB-1 leads to a transient down-regulation of CD28 synthesis and a prolonged unresponsiveness to CD28 signaling. This represents a novel mechanism for regulation of costimulatory signals delivered by interactions of CD28 with the B7/BB-1 counter receptor.

  • Copyright © 1993 by American Association of Immunologists

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The Journal of Immunology
Vol. 150, Issue 8
15 Apr 1993
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CD28 engagement by B7/BB-1 induces transient down-regulation of CD28 synthesis and prolonged unresponsiveness to CD28 signaling.
P S Linsley, J Bradshaw, M Urnes, L Grosmaire, J A Ledbetter
The Journal of Immunology April 15, 1993, 150 (8) 3161-3169;

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CD28 engagement by B7/BB-1 induces transient down-regulation of CD28 synthesis and prolonged unresponsiveness to CD28 signaling.
P S Linsley, J Bradshaw, M Urnes, L Grosmaire, J A Ledbetter
The Journal of Immunology April 15, 1993, 150 (8) 3161-3169;
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Print ISSN 0022-1767        Online ISSN 1550-6606