Lawrence Steinman

Publication Details

  • CRYAB modulates the activation of CD4+ T cells from relapsing-remitting multiple sclerosis patients. Multiple sclerosis (Houndmills, Basingstoke, England) Quach, Q. L., Metz, L. M., Thomas, J. C., Rothbard, J. B., Steinman, L., Ousman, S. S. 2013


    BACKGROUND: Suppression of activation of pathogenic CD4(+) T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. OBJECTIVE: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. METHODS: CD4(+) T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73-92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. RESULTS: The secretion of pro-inflammatory cytokines by CD4(+) T cells was decreased in the presence of CRYAB in a subset of relapsing-remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8(+) T cells, in CD4(+) T cells of MS patients that displayed suppressed cytokine production (responders). CONCLUSION: CRYAB may be capable of suppressing the activation of CD4(+) T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

    View details for PubMedID 23736536

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