CD28 costimulation is crucial for the development of spontaneous autoimmune encephalomyelitis

Area of Science:

• Immunology
• Neuroscience

Background:

• Multiple sclerosis (MS) is a debilitating central nervous system disease.
• Experimental autoimmune encephalomyelitis (EAE) serves as a mouse model for MS.

Purpose of the Study:

• To investigate the role of the T cell costimulatory molecule CD28 in the initiation of spontaneous EAE.
• To determine the mechanism by which CD28 regulates autoimmune pathogenesis in EAE.

Main Methods:

• Utilizing RAG-1-deficient mice transgenic for a myelin basic protein (MBP)-specific T cell receptor (TCR).
• Comparing EAE development in CD28-sufficient and CD28-deficient mice.
• Assessing T cell proliferation and IL-2 production in response to MBP peptide in vitro.

Main Results:

• Spontaneous EAE development in TgMBP+/RAG-1-/- mice necessitates CD28 expression.
• T cells from CD28-deficient mice show proliferation and IL-2 production in vitro, ruling out clonal anergy.
• Autoaggressive T cell proliferation and EAE development are dependent on MBP peptide concentration.

Conclusions:

• CD28 costimulation is critical for in vivo activation of MBP-specific T cells.
• CD28 signaling is essential for the initiation of spontaneous EAE.
• These findings provide the first genetic evidence for CD28's crucial role in EAE pathogenesis.