CD28 costimulation prevents cell death during primary T cell activation

Area of Science:

• Immunology
• Cell Biology

Background:

• CD28 is known to enhance T cell proliferation and effector function.
• Previous studies suggest CD28 costimulation improves human T cell survival.

Purpose of the Study:

• To investigate the role of CD28 in regulating T cell survival.
• To compare T cell survival in wild-type and CD28-deficient mice.

Main Methods:

• Comparing T cell survival characteristics between wild-type and CD28-deficient mice.
• Assessing T cell viability following anti-CD3 activation with and without CD28 costimulation.
• Evaluating the expression of bcl-xL, Bcl-2, and Fas.
• Investigating the role of Fas using lpr animals.
• Analyzing cell death morphology and the effect of ICE protease inhibitors.

Main Results:

• CD28 costimulation augmented T cell viability in wild-type but not CD28-deficient mice.
• CTLA4Ig treatment reduced wild-type T cell viability to levels seen in CD28-deficient cells.
• CD28's enhancement of survival correlated with increased bcl-xL expression.
• No differences in Bcl-2 or Fas expression were observed.
• CD28-dependent survival enhancement was independent of Fas expression.
• Cell death in CD28-deficient or CTLA4Ig-treated mice showed apoptotic characteristics.
• ICE protease inhibitors reversed TCR-induced cell death without CD28 costimulation.

Conclusions:

• CD28 costimulation enhances T cell survival during activation.
• This survival effect is mediated through the up-regulation of bcl-xL.
• The mechanism is independent of Fas expression and involves apoptosis.
• CD28 plays a crucial role in both T cell proliferation and survival post-activation.