期刊
CURRENT GENE THERAPY
卷 7, 期 5, 页码 369-380出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156652307782151443
关键词
hemophilia; autoimmunity; regulatory T cells; retroviral gene therapy
资金
- NHLBI NIH HHS [T32 HL007698] Funding Source: Medline
Tolerance must be maintained to prevent deleterious immune responses. Thus, when tolerance is lost, autoimmunity can result. A number of novel approaches to (re-) induce tolerance for potential clinical applications have been developed in the last decade. Our lab has implemented an immunoglobulin-based gene therapy approach, which may have powerful implications for the treatment of human conditions. These include a variety of autoimmune diseases, transplantation, and the immune response to therapeutic proteins (as in the treatment of hemophilia A) or gene therapy per se. We clone the target (immunogenic) protein in frame with an immunoglobulin heavy chain and deliver it via retrovirus to an activated B cell. In our system, we observe tolerance to multiple epitopes of the protein cloned. An important advantage of this regimen is that identification of the precise peptide epitopes of a target protein is not necessary since selection and presentation by the host's own antigen presenting cells (APC's) eliminates the issue of HLA polymorphism. Additionally, our data indicate that these tolerogenic B cells are stimulating an endogenous population of regulatory T cells, which are effective at suppressing the immune response in both naive and primed hosts. Thus, this approach has potential for future clinical therapy.
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