Cytokine profile and T cell adhesiveness to endothelial selectins: In vivo induction by a myasthenogenic T cell epitope and immunomodulation by a dual altered peptide ligand

Abstract

Myasthenia gravis (MG) is a T cell-regulated antibody-mediated autoimmune disease. Immunization with two myasthenogenic peptides, p195-212 and p259-271, that are sequences of the human acetylcholine receptor α subunit was shown to induce experimental autoimmune MG (EAMG)- associated immune responses. A peptide composed of the two altered peptide ligands (APL) of the myasthenogenic peptides (designated as dual APL) inhibited, in vitro and in vivo, those responses. The objectives of this study were to examine (i) whether in vivo T cell activation by p259-271 affects the cytokine profile and the T cell migration ability, and (ii) whether the latter are immunomodulated by in vivo administration of the dual APL. Our results showed that immunization of mice with p259-271 enriched the population of lymph node and spleen cells with subsets of T cells with strong adhesiveness towards E- and P-selectins. This enrichment was associated with an acquisition of a Th1-type cytokine profile. Treatment of the immunized mice with the dual APL interfered with both the migratory potential of the autoreactive T cells, and the production of the Th1-type cytokines IL-2 and IFN-γ (known to play a pathogenic role in MG and EAMG). T cells derived from APL-treated mice acquired a Th3-type cytokine profile, characterized by the secretion of the immunosuppresive cytokine transforming growth factor-β. Thus, our results suggest that T cell selectin ligands and T cell-derived cytokines are involved in the induction and immunomodulation of EAMG- and MG-associated T cell responses.