期刊
CLINICAL IMMUNOLOGY
卷 104, 期 2, 页码 105-114出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/clim.2002.5258
关键词
APL; immunization; myelin-reactive T cell; antigen-specific therapy; multiple sclerosis
类别
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 MEP 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 IFN-gamma (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. (C) 2002 Elsevier Science (USA).
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