Which T cell types drive the autoimmune response in multiple sclerosis?
Which T cell types drive the autoimmune response in multiple sclerosis?
In multiple sclerosis (MS), the myelin that surrounds the axons of
nerve cells is attacked by the body’s own T cells, resulting in
slowed and disrupted nerve impulses and, ultimately, axon loss.
Myelin basic protein (MBP) is a major component of the myelin sheath
and when used as an antigen will induce experimental autoimmune
encephalitis (EAE) in mice, which is used as an animal model of human
MS.
Interestingly, myelin-specific T cells are found in both healthy
individuals as well as patients with MS, thus researchers have been
working to determine what specific characteristic of these
destructive T cells is dominant in driving the development of EAE/MS.
In a study appearing online on July 12 in advance of publication in
the August print issue of the Journal of Clinical Investigation, Eli
Sercarz and colleagues from the Torrey Pines Institute for Molecular
Studies immunized mice with an epitope of MBP known as Ac1–9, which
resulted in a single episode of EAE in these animals, followed by
recovery and resistance to any reinduction of disease. The authors
then went on to characterize the Ac1–9–specific T cells present
during the induction, onset, and recovery from disease. They
identified two distinct subsets of T cells, or clonotypes, soon after
immunization and prior to disease onset: BV8S2/BJ2S7 and BV16/BJ2S5.
The BV8S2/BJ2S7 clonotype was found in far greater excess,
disappeared with disease recovery, and was found to transfer disease
to other healthy mice. The second clonotype, BV16/BJ2S5, persisted
following recovery, consistent with the hypothesis that the other,
BV8S2/BJ2S7 T cell clonotype, is the driver of disease and necessary
for EAE/MS persistence. The identification of this T cell subset
suggests that these cells may be critical targets valuable to the
design of therapies for autoimmune diseases such as MS.
