CRYAB modulates the activation of CD4 + T cells from relapsing–remitting multiple sclerosis patients

Abstract

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.