We study human autoimmunity; in particular we aim to understand why autoimmunity often occurs during recovery from T cell lymphopenia. People with multiple sclerosis, treated with the highly effective lymphocyte depleting antibody alemtuzumab offer a rare opportunity to study this phenomenon directly in humans, as 1 in 3 patients develop a new autoimmune disease after treatment (mainly thyroid). Using this ?human model? we have shown that rebound T cell reconstitution via the proliferation of cells that have escaped depletion is antagonistic to tolerance. We now ask: 1) Can autoimmunity after alemtuzumab be reduced by promoting T cell production via the thymus? In collaboration with Alasdair Coles, we are testing this approach in an MRC-funded trial (CAMTHY). 2) Why do regulatory T cells (which expand more rapidly than non-Tregs) fail to prevent reconstitution associated autoimmunity? This question forms the basis of a Wellcome-Trust funded project.