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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/3587

Title: IN-VIVO CLONOTYPIC REGULATION OF HUMAN MYELIN BASIC PROTEIN-REACTIVE T-CELLS BY T-CELL VACCINATION
Authors: Zhang, JK
VANDEVYVER, Caroline
STINISSEN, Piet
RAUS, Jef
Issue Date: 1995
Publisher: AMER ASSOC IMMUNOLOGISTS
Citation: JOURNAL OF IMMUNOLOGY, 155(12). p. 5868-5877
Abstract: Autoreactive T cells specific for myelin basic protein (MBP) are implicated in the pathogenesis of multiple sclerosis, The mechanism by which MBP-reactive T cells are regulated in vivo remains unknown, but is thought to involve the clonotypic regulatory network that can be induced by immunization with attenuated T cells and TCR peptides, We reported previously that immunization of multiple sclerosis patients with irradiated MBP-reactive T tells (T cell vaccination) induced T cell responses to the immunizing clones, resulting in a clonal depletion of circulating MBP-reactive T cells, In this study, we demonstrated that in the majority of the recipients, MBP-reactive T cells remained undetectable in circulation over a period of 1 to 3 yr after vaccination, while they reappeared in some individuals (three of nine), coinciding with clinical exacerbation, The reappearing MBP-reactive T cells were found to originate from clonal origins different from those of T cells persisting before immunization, suggesting a shift of the T cell repertoire to other determinants of MBP. The immunization induces predominantly CD8(+) regulatory T cells capable of lysing the immunizing clones in a clonotype-specific manner, The T cell responses induced by immunization were restricted to the immunizing clones and did not affect MBP-reactive clones not used for immunization, Our data further suggest that different hypervariable regions of the TCR may be involved in the observed clonotypic interaction, This study provides useful information for designing future clinical trials using T cell vaccination and other TCR-based therapeutic strategies.
Notes: DR WILLEMS INST,BIOTECHNOL UNIT,B-3590 DIEPENBEEK,BELGIUM. LIMBURGS UNIV CENTRUM,DIEPENBEEK,BELGIUM.ZHANG, JW, DR WILLEMS INST,MULTIPLE SCLEROSIS RES & IMMUNOL UNIT,UNIV CAMPUS,B-3590 DIEPENBEEK,BELGIUM.
URI: http://hdl.handle.net/1942/3587
Link to publication: http://www.jimmunol.org/cgi/content/abstract/155/12/5868
ISI #: A1995TJ63100053
ISSN: 0022-1767
Type: Journal Contribution
Appears in Collections: Research publications

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