• Home
  • Search Results
  • Immunogenicity of human mesenchymal stem cells in HLA-class I-restricted T-cell responses against viral or tumor-associated antigens.

Immunogenicity of human mesenchymal stem cells in HLA-class I-restricted T-cell responses against viral or tumor-associated antigens.

Stem cells (Dayton, Ohio) (2008-02-23)
Fabio Morandi, Lizzia Raffaghello, Giovanna Bianchi, Francesca Meloni, Annalisa Salis, Enrico Millo, Soldano Ferrone, Vincenzo Barnaba, Vito Pistoia
ABSTRACT

Human mesenchymal stem cells (MSC) are immunosuppressive and poorly immunogenic but may act as antigen-presenting cells (APC) for CD4(+) T-cell responses; here we have investigated their ability to serve as APC for in vitro CD8(+) T-cell responses. MSC pulsed with peptides from viral antigens evoked interferon (IFN)-gamma and Granzyme B secretion in specific cytotoxic T lymphocytes (CTL) and were lysed, although with low efficiency. MSC transfected with tumor mRNA or infected with a viral vector carrying the Hepatitis C virus NS3Ag gene induced cytokine release but were not killed by specific CTL, even following pretreatment with IFN-gamma. To investigate the mechanisms involved in MSC resistance to CTL-mediated lysis, we analyzed expression of human leukocyte antigen (HLA) class I-related antigen-processing machinery (APM) components and of immunosuppressive HLA-G molecules in MSC. The LMP7, LMP10, and ERp57 components were not expressed and the MB-1 and zeta molecules were downregulated in MSC either unmanipulated or pretreated with IFN-gamma. Surface HLA-G was constitutively expressed on MSC but was not involved in their protection from CTL-mediated lysis. MSC supernatants containing soluble HLA-G (sHLA-G) inhibited CTL-mediated lysis, whereas those lacking sHLA-G did not. The role of sHLA-G in such inhibition was unambiguously demonstrated by partial restoration of lysis following sHLA-G depletion from MSC supernatants. In conclusion, human MSC can process and present HLA class I-restricted viral or tumor antigens to specific CTL with a limited efficiency, likely because of some defects in APM components. However, they are protected from CTL-mediated lysis through a mechanism that is partly sHLA-G-dependent.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Phosphate buffered saline, tablet
Sigma-Aldrich
Phosphate buffered saline, powder, pH 7.4, for preparing 1 L solutions
Sigma-Aldrich
Phosphate buffered saline, 10× concentrate, BioPerformance Certified, suitable for cell culture
Sigma-Aldrich
Phosphate Buffered Saline with 0.05% TWEEN® 20, pH 7.4
Sigma-Aldrich
Phosphate buffered saline, BioPerformance Certified, pH 7.4
Sigma-Aldrich
3,3′,5,5′-Tetramethylbenzidine, ≥99%
Sigma-Aldrich
Phosphate Buffered Saline, 10× PBS for Western blots and IP
Sigma-Aldrich
Phosphate buffered saline, powder, pH 7.4, for preparing 5 L solutions
Sigma-Aldrich
Phosphate buffered saline, pH 7.2 (25 °C)
Sigma-Aldrich
3,3′,5,5′-Tetramethylbenzidine, ≥98% (TLC)
Sigma-Aldrich
Phosphate buffered saline, BioUltra, pH 7.4 ( in solution), contains TWEEN 20, tablet
Sigma-Aldrich
Phosphate buffered saline, pH 7.4, contains BSA, powder
Sigma-Aldrich
3,3′,5,5′-Tetramethylbenzidine, ≥98.0% (NT)
Sigma-Aldrich
Phosphate buffered saline, BioUltra, washing buffer for peroxidase conjugates in Western Blotting, 10x concentrate
Sigma-Aldrich
Phosphate buffered saline, BioUltra, solution
Sigma-Aldrich
Phosphate Buffered Saline with 3% Non-Fat Milk, pH 7.4
Sigma-Aldrich
3,3′,5,5′-Tetramethylbenzidine, tablet, 1 mg substrate per tablet
Sigma-Aldrich
Phosphate buffered saline, Autoclaved, pH 7.2 (25 °C)
Sigma-Aldrich
Phosphate buffered saline, with 5% nonfat milk, powder (dry milled), pH 7.3
Sigma-Aldrich
Phosphate buffered saline, pH 7.6 (25 °C)
Supelco
3,3′,5,5′-Tetramethylbenzidine, standard for GC