|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
4
|
|
pubmed:dateCreated |
1995-4-10
|
|
pubmed:abstractText |
Recombinant adenoviruses are an attractive vehicle for gene therapy to the lung in the treatment of cystic fibrosis (CF). First-generation viruses deleted of E1a and E1b transduce genes into airway epithelial cells in vivo; however, expression of the transgene is transient and associated with substantial inflammatory responses, and gene transfer is significantly reduced following a second administration of the virus. In this study, we have used mice deficient in immunological effector functions in combination with adoptive and passive transfer techniques to define antigen-specific cellular and humoral immune responses that underlie these important limitations. Our studies indicate that major histocompatibility complex class I-restricted CD8+ cytotoxic T lymphocytes are activated in response to newly synthesized antigens, leading to destruction of virus infected cells and loss of transgene expression. Major histocompatibility complex class II-associated presentation of exogenous viral antigens activates CD4+ T-helper (TH) cells of the TH1 subset and, to a lesser extent, of the TH2 subset. CD4+ cell-mediated responses are insufficient in the absence of cytotoxic T cells to completely eliminate transgene containing cells; however, they contribute to the formation of neutralizing antibodies in the airway which block subsequent adenovirus-mediated gene transfer. Definition of immunological barriers to gene therapy of cystic fibrosis should facilitate the design of rational strategies to overcome them.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-1284642,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-1285365,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-1309887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-1370653,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-1375392,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-1547487,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-1827819,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-1910207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-2139497,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-2785954,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-6547205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-7509347,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-7514445,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-7522742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-7526382,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-7533647,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-7685107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-7685651,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-7692307,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-7849095,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-7904900,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-8016137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-8035532,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-8116236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-8183921,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-8228800,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-8293464,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-8298650,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7884845-8380066
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Apr
|
|
pubmed:issn |
0022-538X
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
69
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2004-15
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:7884845-Adenoviridae,
pubmed-meshheading:7884845-Animals,
pubmed-meshheading:7884845-Antibodies, Viral,
pubmed-meshheading:7884845-Antigens, Viral,
pubmed-meshheading:7884845-Cystic Fibrosis,
pubmed-meshheading:7884845-Disease Models, Animal,
pubmed-meshheading:7884845-Gene Therapy,
pubmed-meshheading:7884845-Gene Transfer Techniques,
pubmed-meshheading:7884845-Genetic Vectors,
pubmed-meshheading:7884845-Histocompatibility Antigens Class I,
pubmed-meshheading:7884845-Immunity, Cellular,
pubmed-meshheading:7884845-Mice,
pubmed-meshheading:7884845-Mice, Inbred C57BL,
pubmed-meshheading:7884845-Mice, Transgenic,
pubmed-meshheading:7884845-Neutralization Tests,
pubmed-meshheading:7884845-Pneumonia,
pubmed-meshheading:7884845-Recombination, Genetic,
pubmed-meshheading:7884845-T-Lymphocyte Subsets,
pubmed-meshheading:7884845-T-Lymphocytes, Cytotoxic
|
|
pubmed:year |
1995
|
|
pubmed:articleTitle |
Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses.
|
|
pubmed:affiliation |
Institute for Human Gene Therapy, University of Pennsylvania Medical Center, Philadelphia 19104.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
