In Vivo Activation of Myelin Oligodendrocyte Glycoprotein-Specific T Cells in Healthy Control Subjects

Autoreactive T cells are present in healthy subjects but are assumed not to induce overt disease due to lack of exposure to autoantigen or because of immune regulation. In EAE, activation of myelin protein-specific T cells is a crucial step in disease induction. In this study, we evaluated whether myelin oligodendrocyte glycoprotein (MOG)-reactive T cells had been activated in vivo using peripheral blood mononuclear cells from neurologically healthy subjects. In vitro assays used either memory, CD45RO+, or naı̈ve, CD45RA+ T-cell populations. MOG-reactive T cells were isolated from 7 of 10 subjects. Unexpectedly, a substantial number of MOG-reactive T cells were isolated from the CD45RO+, memory T-cell subset in 6 subjects. The majority of these T cells generated γ interferon in excess of IL-4, expressed VLA-4, and produced nerve growth factor. These findings demonstrate that a substantial proportion of MOG-reactive T cells from some subjects have been activated in vivo without resulting in clinical disease.