J Autoimmun 2003 Feb;20(1):71-81
Oliveira EM, Bar-Or A, Waliszewska AI, Cai G, Anderson DE, Krieger JI, Hafler DA.
Laboratory of Molecular and Cellular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, thought to be mediated in part by an autoimmune response of T cells to protein components of the myelin sheath.
The reaction of nai;ve T cells against these antigens requires co-stimulation through CD28.
However, the proliferative response of peripheral blood mononuclear cells isolated from patients with MS and stimulated with myelin basic protein (MBP) has been shown to be relatively independent of B7-CD28 co-stimulation, suggesting that dysregulation of co-stimulatory pathways may be involved in the pathogenesis of MS.
Here, the role of CTLA-4 engagement was investigated.
As expected, blocking CTLA-4-mediated signaling during stimulation of MBP-reactive T cells from healthy controls enhanced the proliferative and cytokine responses.
In contrast, CTLA-4 blockade had less effect in patients with MS, suggesting that at least two regulatory mechanisms may be impaired in these individuals.
Understanding how co-stimulatory signals may be dysregulated in patients with MS is important at a time when targeting of these pathways is being developed.