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Author Fink, Annette ♦ Lemmermann, Niels A. W. ♦ Gillert Marien, Dorothea ♦ Thomas, Doris ♦ Freitag, Kirsten ♦ Böhm, Verena ♦ Wilhelmi, Vanessa ♦ Reifenberg, Kurt ♦ Reddehase, Matthias J. ♦ Holtappels, Rafaela
Source SpringerLink
Content type Text
Publisher Springer-Verlag
File Format PDF
Copyright Year ©2012
Language English
Subject Domain (in DDC) Technology ♦ Medicine & health
Subject Keyword Antigen presentation ♦ CD8 T cells ♦ Cytomegalovirus ♦ Hematopoietic cell transplantation (HCT) ♦ Immunotherapy ♦ Immune evasion ♦ IFN-γ transgenic mice ♦ Interferon-γ ♦ MHC class I ♦ Medical Microbiology ♦ Immunology
Abstract Cytomegalovirus (CMV) disease with multiple organ manifestations is the most feared viral complication limiting the success of hematopoietic cell transplantation as a therapy of hematopoietic malignancies. A timely endogenous reconstitution of CD8 T cells controls CMV infection, and adoptive transfer of antiviral CD8 T cells is a therapeutic option to prevent CMV disease by bridging the gap between an early CMV reactivation and delayed endogenous reconstitution of protective immunity. Preclinical research in murine models has provided ‘proof of concept’ for CD8 T-cell therapy of CMV disease. Protection by CD8 T cells appears to be in conflict with the finding that CMVs encode proteins that inhibit antigen presentation to CD8 T cells by interfering with the constitutive trafficking of peptide-loaded MHC class I molecules (pMHC-I complexes) to the cell surface. Here, we have systematically explored antigen presentation in the presence of the three currently noted immune evasion proteins of murine CMV in all possible combinations and its modulation by pre-treatment of cells with interferon-gamma (IFN-γ). The data reveal improvement in antigen processing by pre-treatment with IFN-γ can almost overrule the inhibitory function of immune evasion molecules in terms of pMHC-I expression levels capable of triggering most of the specific CD8 T cells, though the intensity of stimulation did not retrieve their full functional capacity. Notably, an in vivo conditioning of host tissue cells with IFN-γ in adoptive cell transfer recipients constitutively overexpressing IFN-γ (B6-SAP-IFN-γ mice) enhanced the antiviral efficiency of CD8 T cells in this transgenic cytoimmunotherapy model.
ISSN 03008584
Age Range 18 to 22 years ♦ above 22 year
Educational Use Research
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2012-09-09
Publisher Place Berlin/Heidelberg
e-ISSN 14321831
Journal Medical Microbiology and Immunology
Volume Number 201
Issue Number 4
Page Count 13
Starting Page 513
Ending Page 525


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Source: SpringerLink