By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Investigators discuss new findings in Immunology. According to news originating from Providence, Rhode Island, by NewsRx correspondents, research stated, "Immune responses directed against viral capsid proteins constitute a main safety concern in the use of adeno-associated virus (AAV) as gene transfer vectors in humans. Pharmacological immunosuppression has been proposed as a solution to the problem; however, the approach suffers from several potential limitations."
Our news journalists obtained a quote from the research from the University of Rhode Island, "Using MHC class II epitopes initially identified within human IgG, named Tregitopes, we showed that it is possible to modulate CD8(+) T cell responses to several viral antigens in vitro. We showed that incubation of peripheral blood mononuclear cells with these epitopes triggers proliferation of CD4(+)CD25(+)FoxP3(+) T cells that suppress killing of target cells loaded with MHC class I antigens in an antigen-specific fashion, through a mechanism that seems to require cell-to-cell contact. Expression of a construct encoding for the AAV capsid structural protein fused to Tregitopes resulted in reduction of CD8(+) T cell reactivity against the AAV capsid following immunization with an adenoviral vector expressing capsid. This was accompanied by an increase in frequency of CD4(+)CD25(+)FoxP3(+) T cells in spleens and lower levels of inflammatory infiltrates in injected tissues."
According to the news editors, the research concluded: "This proof-of-concept study demonstrates modulation of CD8(+) T cell reactivity to an antigen using regulatory T cell epitopes is possible."
For more information on this research see: Modulation of CD8(+) T cell responses to AAV vectors with IgG-derived MHC class II epitopes. Molecular Therapy, 2013;21(9):1727-1737. Molecular Therapy can be contacted at: Nature Publishing Group, 75 Varick St, 9TH Flr, New York, NY 10013-1917, USA. (Elsevier - www.elsevier.com; Molecular Therapy - www.elsevier.com/wps/product/cws_home/622922)
The news correspondents report that additional information may be obtained from D.J. Hui, University of Rhode Island, Inst Immunol & Informat, Providence, RI 02908, United States. Additional authors for this research include E. Basner-Tschakarjan, Y.F. Chen, R.J. Davidson, G. Buchlis, M. Yazicioglu, G.C. Pien, J.D. Finn, V. Haurigot, A. Tai, D.W. Scott, L.P. Cousens, S.Z. Zhou, A.S. De Groot and F. Mingozzi (see also Immunology).
Keywords for this news article include: Biotechnology, Virion, Epitopes, Providence, Immunology, CD Antigens, Rhode Island, CD4 Antigens, CD8 Antigens, Gene Therapy, Nucleocapsid, United States, HIV Receptors, Bioengineering, Differentiation, Membrane Proteins, Biological Factors, T-Lymphocyte Antigens, Interleukin-16 Receptors, North and Central America
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