Published online 28 February 2005 doi:10.1084/jem2015iti3
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 5, 663-664
Out with the old, in with the new
Muraro et al., reporting on page 805, use stem cell transplants to suppress active multiple sclerosis (MS), and then show that the treatment increased the number of naive T cells at the expense of the memory T cells that are associated with disease.
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An MS lesion (arrow) was resolved two years after stem cell transplantation.
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Intense immunosuppression followed by stem cell transplantation has been shown to slow or stop the formation of new brain lesions in up to 95% of patients with aggressive MS. Yet it has been controversial and rarely used, mainly because immunosuppression is risky and because nothing was known about how transplantation induced remission. One proposed theory was that transplantation might change the composition of the T cell pool and bias it away from autoreactivity.
Muraro and colleagues now provide the first evidence that stem cell transplantation allows patients to regenerate a new repertoire of T cells that are less activated and more diverse than their pretransplant repertoires. This suggests that many of the disease-causing T cells—most of which have a memory phenotype—were eliminated by the treatment.
However, concrete proof that autoreactive T cells are reduced or eliminated is difficult to obtain, partly because the specificities of the autoreactive T cells that invade the central nervous system are not well defined.
The difficulty in assessing the basis for treatment success is one problem. Another is the possibility that autoreactive cells will reemerge from the pool of transferred stem cells. The authors agree that these cells could eventually come back, but hope that resetting the immune system may improve the quality of life for patients with an otherwise poor prognosis.
They emphasize, however, that this intense therapy is probably only suited to a subset of MS patients who have active and aggressive disease and that its implementation will require careful patient selection.
Heather L. Van Epps
hvanepps{at}rockefeller.edu
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Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients
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