Alemtuzumab is a humanized monoclonal antibody specific for the CD52 protein present at high levels on the surface of B and T lymphocytes. In clinical trials, alemtuzumab has shown a clinical benefit superior to that of interferon beta in relapsing-remitting multiple sclerosis (RRMS) patients. Treatment with alemtuzumab leads to the depletion of circulating lymphocytes followed by a repopulation process characterized by alterations in the number, proportions and properties of lymphocyte subsets. Of particular interest, an increase in the percentage of T cells with a regulatory phenotype (Tregs) has been observed in MS patients post-alemtuzumab. Since Tregs play an important role in the control of autoimmune responses, the effect of alemtuzumab on Tregs was further studied in vitro. Alemtuzumab effectively mediated complement-dependent cytolysis (CDC) of human T lymphocytes and the remaining population was enriched in T cells with a regulatory phenotype. The alemtuzumab-exposed T cells displayed functional regulatory characteristics including anergy to stimulation with allogeneic dendritic cells and ability to suppress the allogeneic response of autologous T cells. Consistent with the observed increase in Treg frequency, the CD25hi T cell population was necessary for the suppressive activity of alemtuzumab-exposed T cells. The mechanism of this suppression was found to be dependent on both cell-cell contact and IL-2 consumption. These findings suggest that an alemtuzumab-mediated increase in the proportion of Tregs may play a role in promoting the long term efficacy of alemtuzumab in MS patients.
Tregs are immunological flavour of the month and this study suggests that Lemtrada may help by promoting T regulatory cell
function, thought to limit the generation of autoimmunity, in addition to causing long-term depletion of other white blood cells. These may help stop MS return but one could also ask why then to MSers get secondary autoimmunities as a consequence of alemtuzumab?