Autoimmune neurologic diseases
Immunoglobulin Like Transcript 3 (ILT3) also called LILRB4, LIR-5, CD85k, a member of the leukocyte immunoglobulin like receptors, is a marker of human tolerogenic dendritic cells which induce anergy in T helper cells and elicit the differentiation of CD8 T suppressor cells. The recombinant ILT3.Fc protein engineered from the extracellular Ig like domains of ILT3 binds to its ligand CD166/ALCAM suppressing human T cell effector function both in vitro and in vivo. We found that ILT3.Fc also binds to the mouse CD166+ immune cells. Therefore, we explored the immunotherapeutic potency of ILT3.Fc in the classical model of MOG 35-55 peptide-induced-EAE in C57BL/6 mice. Treatment was initiated at the time of immunization or 5 days thereafter. A significant delay of disease onset, progression to partial or complete paralysis and increased survival was achieved in mice treated with ILT3.Fc. T cells from control mice proliferated strongly and produced large amounts of IFN-γ and IL-17A in response to MOG 35-55 peptide while ILT3.Fc treated mice showed significantly lower responses. Flow cytometry and PCR studies indicated that IL-4, TNF, IL-6, IL-10 and IL-2 were also inhibited in cells from spinal cord, lymph nodes or spleen of ILT3.Fc treated mice. Neuropathological studies showed a reduction in inflammatory infiltrates and demyelinated areas in brains and spinal cords of treated mice. ILT3.Fc induced CD8+ mouse T suppressor cells and anergy in CD4+ T helper cells when added to in vitro activated cultures, suggesting its potential immunotherapeutic value.