Clin Immunol 2002 Aug;104(2):105
Kim H, Antel J, Duquette P, Alleva D, Conlon P, Bar-Or A.
Neuroimmunology Unit, Department of Neurology, Montreal Neurological Institute, McGill University, Montreal, Canada
Altered peptide ligands (APLs) can modulate responses of T cells to native peptide antigens implicated in the pathogenesis of autoimmune diseases.
An APL of the putative target antigen myelin basic protein (MBP) peptide 83-99 has been used in abbreviated clinical trials in patients with multiple sclerosis (MS).
Our objective was to assess the long-term persistence, and characteristics, of the APL-induced immune response in such patients.
We measured the ex vivo proliferative frequency to the APL and native MBP, the cross-reactivity, and the cytokine production by these lines.
We found that a 4- to 16-week course of APL therapy could induce a persistent (2-4.5 year) increase in the frequency of T cells responsive to both the APL and the native MBP in a select number of patients.
These T cells produced high levels of IL-5, contrasting with the pretreatment observation that the responses to either antigen were IFNgamma (Th1) dominant.
Our results indicate that APL therapy can induce persistent Th2-directed immune deviation.
Understanding the impact of such APL-induced immune responses on MS disease activity will require additional clinical trials that incorporate careful monitoring of both clinical and immunological parameters.