Costimulation of human CD28– T cells by 4-1BB ligand

✍ Scribed by Jacob Bukczynski; Tao Wen; Tania H. Watts

• Book ID: 102279328
• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 305 KB
• Volume: 33
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/immu.200310020

✦ Synopsis

Abstract

The T cell surface protein CD28 provides a critical costimulatory signal for T cell activation. With age, humans accumulate increasing numbers of CD28^–^ T cells, and this loss of CD28 expression is exacerbated certain disease states, such as HIV infection, autoimmune conditions or cancer. It is unclear whether CD28^–^ T cells represent terminally differentiated effector cells or whether they remain sensitive to costimulation by CD28‐independent pathways. Here, we demonstrate that 4–1BB ligand can costimulate human CD28^–^ T cells, resulting in cell division, inflammatory cytokine production, increased perforin levels, enhancement of cytolytic effector function, as well as the up‐regulation of the anti‐apoptotic protein Bcl‐X~L~. Thus, human CD28^–^ T cells can respond to costimulatory signals and as such become attractive targets for therapeutic intervention, particularly in chronic infectious and inflammatory diseases where large numbers of these cells accumulate.