Nature Medicine
2, 1354 - 1360 (1996)
doi:10.1038/nm1296-1354
Defective post−thymic tolerance mechanisms during the chronic progressive stage of multiple sclerosisJorge Correale1, 2, 4, Wendy Gilmore1, 3, Jerome Lopez1, Si Q. Li1, Minnie McMillan1, 2
& Leslie P. Weiner1, 2
1Department of Neurology, University of Southern California, School of Medicine 1333 San Pablo Street, MCK 142, Los Angeles, California 90033, USA
2Department of Molecular Microbiology and Immunology, University of Southern California, School of Medicine 1333 San Pablo Street, MCK 142, Los Angeles, California 90033, USA
3Department Cell and Neurobiology, University of Southern California, School of Medicine 1333 San Pablo Street, MCK 142, Los Angeles, California 90033, USA
4Correspondence should be addressed to J.C. We have recently isolated a panel of T−cell clones from chronic progressive multiple sclerosis (MS) patients that are capable of functioning as antigen−presenting cells and of expressing the costimulatory molecules B7−1 and B7−2. In this report we show that these T−cell clones are resistant to inhibitory regulation, including the induction of anergy and sensitivity to tumor growth factor− (TGF−)−induced growth inhibition. The resistance to anergy induction was associated with expression of B7 costimulatory molecules. These data suggest that lack of responsiveness to peripheral inhibitory signals may account for the entry of autoimmune diseases into a chronic progressive phase.
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