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T-cells play a central role in the pathogenesis of multiple sclerosis (MS). Altered peptide ligands (APLs) have most commonly been used as T-cell receptor (TCR) ligands, to alter T-cell responses to presumed immunogenic or target antigens. The treatment therapies targeting T-cells non-specifically are: lymphocytapheresis, total lymphoid irradiation, anti-CD4 antibody, anti-CD3 antibody, anti-CD154 antibody, CTLA4Ig, interleukin-12, tumor necrosis factor alpha, interferon gamma and transforming growth factor beta. Although the T-cell is not the primary target of several drugs that are currently approved or are under investigation for the treatment of MS, many of these therapies have secondary effects on T-cell measures. The T-cell is an important target in MS therapeutics. The success of several drugs that specifically target the T-cell and T-cell responses reinforces this point. Further success of T-cell directed therapies depends on the appropriate targeting of phases of T-cell activation and function and the accurate identification of antigens.