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CD28 and apoptosis
L H Boise1, P J Noel, C B Thompson
1Howard Hughes Medical Institute, University of Chicago, IL 60637-5420, USA.
Abstract:
Until recently, it was thought that signal transduction through CD28 and the related molecule CTLA4 prevented the induction of anergy in T cells activated through the TCR. This hypothesis has been suggested as an explanation for how soluble forms of CTLA4, which bind the CD28/CTLA4 ligands B7-1 and B7-2, can prevent graft rejection. Recent reports suggest that another function of CD28 costimulation is the regulation of T-cell survival. CD28 not only enhances IL-2 production, which can act as an extrinsic regulator of cell survival, but also augments the expression of the intrinsic survival factor Bcl-xL. In contrast, CTLA4-mediated signal transduction has been reported to induce cell death in previously activated T cells. These data suggest that B7-1/B7-2 signaling not only controls cell proliferation and T-helper cell subset selection, but also T-cell survival.
Insights
Signal transduction via CD28 and CTLA4 molecules plays a crucial role in T-cell activation and survival. This signaling pathway influences T-cell proliferation, subset selection, and prevents graft rejection by regulating cell death.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Signaling
Background:
- T-cell activation and anergy are regulated by signal transduction pathways involving CD28 and CTLA4.
- Soluble CTLA4 has been implicated in preventing graft rejection by binding B7-1 and B7-2 ligands.
- The role of CD28 costimulation in T-cell survival was recently investigated.
Purpose of the Study:
- To investigate the role of CD28 costimulation in regulating T-cell survival.
- To explore the contrasting effects of CD28 and CTLA4 signaling on T-cell fate.
- To understand how B7-1/B7-2 signaling impacts T-cell proliferation, subset selection, and survival.
Main Methods:
- Analysis of signal transduction pathways involving CD28 and CTLA4.
- Investigating the effects of CD28 costimulation on IL-2 production and Bcl-xL expression.
- Examining CTLA4-mediated signal transduction in previously activated T cells.
Main Results:
- CD28 costimulation enhances IL-2 production and augments Bcl-xL expression, promoting T-cell survival.
- CTLA4-mediated signal transduction has been reported to induce cell death in activated T cells.
- B7-1/B7-2 signaling influences T-cell proliferation, T-helper cell subset selection, and T-cell survival.
Conclusions:
- CD28 and CTLA4 signaling have distinct roles in regulating T-cell fate, impacting survival and proliferation.
- B7-1/B7-2 interactions are critical regulators of T-cell responses beyond just proliferation and subset selection.
- Understanding these pathways is crucial for controlling immune responses and preventing graft rejection.