Correction of defective expression in MHC class II deficiency (bare lymphocyte syndrome) cells by retroviral transduction of CIITA Journal Article


Authors: Bradley, M. B.; Fernandez, J. M.; Ungers, G.; Diaz-Barrientos, T.; Steimle, V.; Mach, B.; O'Reilly, R.; Lee, J. S.
Article Title: Correction of defective expression in MHC class II deficiency (bare lymphocyte syndrome) cells by retroviral transduction of CIITA
Abstract: Retrovirus-mediated gene transfer was used to restore expression to MHC class II-negative patient cells from complementation group A(II) of MHC class II immunodeficiency or bare lymphocyte syndrome (BLS). The cells of these patients do not transcribe MHC class II genes due to a defect in the trans-acting factor, CIITA. We constructed a vector, pGAG/Ii-CIITA, with the MHC class II-associated invariant chain promoter driving CIITA expression. Cocultivation with the virus producer line was consistently shown to be the optimal method for infection of all cell types. The induction of MHC class II expression after virus infection was rapid, and high levels of expression were achieved in cell lines within 1 wk of infection. In addition, expression was easily detectable even in peripheral blood cells of a BLS patient within a few days. Cell lines maintained in vitro for several months remained positive, and the proportion of cells with surface expression of DR was correlated with the number of integrated proviruses. Moreover, transduced B lymphoblastoid cell lines readily established tumors in CB17-scid/scid mice, and the MHC class II-positive cells demonstrated a clear competitive advantage in vivo. Ultimately, we hope to use this transduction system to restore normal immune function to a BLS patient for which no other therapeutic option currently exists.
Keywords: genetics; gene; nuclear protein; gene transfer; gene vector; genetic vectors; nuclear proteins; biosynthesis; immunology; transactivator protein; hla antigen class 2; hla dr antigen; hla-dr antigens; organ specificity; gene therapy; antibody specificity; trans-activators; histocompatibility antigens class ii; genes, mhc class ii; combined immunodeficiency; severe combined immunodeficiency; retrovirus; retroviridae; gene transfer techniques; gag protein; b lymphocyte antigen; invariant chain; antigens, differentiation, b-lymphocyte; gene products, gag; humans; human; article; mhc class ii transactivator protein
Journal Title: Journal of Immunology
Volume: 159
Issue: 3
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 1997-08-01
Start Page: 1086
End Page: 1095
Language: English
PUBMED: 9233601
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Richard O'Reilly
    748 O'Reilly
  2. Janet   Lee
    34 Lee