Immunomodulation 2Friday, October 15, 2010, 15:30 - 17:00
Epicutaneous immunisation with myelin peptides induces a unique population of tolerogenic dendritic cells in lymph nodes of multiple sclerosis patientsM. Jurynczyk, A. Walczak, A. Jurewicz, D. Jesionek-Kupnicka, M. Szczepanik, K. Selmaj (Lodz, Cracow, PL)
Antigen-specific therapy in multiple sclerosis is aimed at selective inhibition of autoimmune myelin-reactive responses. Key autoantigens in MS include myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). Epicutaneous application of myelin peptides has proven to be effective in induction of antigen-specific immune tolerance in experimental models of MS.
We have conducted a one-year placebo-controlled clinical study of myelin peptides (MBP85-99, PLP139-151 and MOG35-55) applied in a mixture to the skin of patients with relapsing-remitting MS patients. In subjects participating in the study (n = 30) we examined immune responses in the skin, lymph nodes and peripheral blood immune cells.
In the skin at the site of immunization in patients treated epicutaneously with myelin peptides we found dendritic Langerhans cells showing an activated phenotype with enlarged cell bodies and extensive CD1a staining. In local lymph nodes of myelin-peptide-treated patients we detected a unique population of large, highly granular cells that was absent in the placebo group. All of these cells were found to be CD11c+ dendritic cells. A subset of these cells also expressed HLA-DR, -DP, -DQ suggesting a capacity for antigen presentation. Induction of this population was accompanied in the peripheral blood by the generation of type 1, IL-10 producing regulatory T cells, suppression of specific autoreactive proliferative responses and suppression of IFN-gamma and TGF-beta production.
We demonstrated that epicutaneous immunization with myelin peptides generates a unique population of tolerogenic dendritic cells in local lymph nodes and attenuates autoimmunity in MS patients.
The authors have nothing to disclose.