Immediate induction of enhanced CD8 suppressive function following glatiramer acetate therapy in multiple sclerosis (164.20)

Multiple Sclerosis (MS) is an immune-mediated, demyelinating disorder of the CNS. Glatiramer acetate (GA/Copaxone) is an FDA-approved treatment for relapsing-remitting MS that induces functional changes in antigen-presenting cells (APC) and CD4 and CD8 T-cells. We have previously shown that treatment-naïve MS patients have deficient CD8 T-cell responses to GA, which are restored after GA therapy. This is associated with enhanced cytotoxic/suppressive function in these cells. In this study, we assessed the immediate immunologic changes induced by GA therapy in treatment-naïve MS patients by multiparametric monitoring of T-cell and APC subsets prior to and at 4, 12, 24, 72 hrs of treatment. In untreated healthy control subjects quantitative and functional readouts showed stable dynamics over time. MS patients showed greater proportions of memory/effector CD4 and CD8 populations at baseline, which did not vary. Similarly, cytokine production by APC subsets was also stable. Interestingly, as early as 4 to 12 hrs after the initial GA injection, we observed significantly enhanced suppressive ability in CD8 T-cells. This rapid functional change consistently occurred in GA, as well as an IFN-b-treated control cohort. These studies show that the induction of T-cell suppressive function is an important early event during therapy. Future studies will delineate whether these changes are predictive of sustained longterm immunologic and clinical responsiveness.