MHC class I-cestricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses

Yang, Yiping; Ertl, Hildegund C.J.; Wilson, James M.

doi:10.1016/1074-7613(94)90074-4

Cited by 597 publications

(449 citation statements)

References 28 publications

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“…Viral vector transduction, however, is actually an abortive infection of the target tissue. Viral vectors, and particularly adenovirus vectors, induce potent host inflammatory and immune responses that limit gene expression and generate significant tissue damage or morbidity (30,31). The events involved in virus entry into a cell activate a number of second messenger pathways and signaling molecules.…”

Section: Discussionmentioning

confidence: 99%

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Chen

Ding

Schröppel

et al. 2003

American Journal of Transplantation

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Transplantation of allogeneic grafts presents several challenges to the innate and adaptive immune systems including chemokine leukocyte recruitment, activation, and effector function. We defined the chemokines and receptors induced by the transplant procedure/ischemia injury, alloantigen and gene transfer vector administration in murine cardiac grafts. E1, E3 deleted AdRSVbgal was transferred into grafts at the time of transplantation, grafts were harvested after 1-14 days, and a pathway-specific cDNA array was used to evaluate the levels of 67 chemokine and chemokine receptor genes. Transplantation resulted in ischemic injury and induction of a number of similar genes in both the syngeneic and allogeneic grafts, such as CXCL1 and CXCL5, which increased dramatically on day 1 and returned rapidly to baseline in the syngeneic grafts. Alloantigen stimulated the adaptive immune response and induced the presence of more inflammatory genes within the grafts, particularly at later time points. The adenovirus vector induced a broader panel of genes, among them potent inflammatory chemokines CXCL9 and CXCL10, that are induced earlier or more strongly compared with alloantigen stimulation alone. As alloantigen and adenovirus vectors both induce similar sets of genes, targeting these molecules may not only inhibit alloimmunity, but also enhance the utility of the gene transfer vector.

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Section: Discussionmentioning

confidence: 99%

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Chen

Ding

Schröppel

et al. 2003

American Journal of Transplantation

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“…In peripheral tissues, direct cytotoxicity of transduced cells has been described in some, [68][69][70][71] but not in all experimental paradigms. 72 Thus, the phenomenological response detected in the brain upon activation of systemic immunity depends on the antigen.…”

Section: Efferent Responsesmentioning

confidence: 99%

Inflammation and adaptive immune responses to adenoviral vectors injected into the brain: peculiarities, mechanisms, and consequences

Löwenstein

Castro

2003

Gene Ther

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“…Unfortunately, as is now well established, first-generation adenovirus vectors elicit strong cellular immune responses against the cells that they have transduced. [1][2][3][4] Because this immunogenicity is largely a consequence of the low-level expression of virus genes that remain in the vector backbone, one approach to overcoming this immune response has been to engineer these vectors further to remove additional virus genes, especially other early regions such as E2 and E4. [5][6][7][8][9][10][11][12][13][14] Although some studies have indicated that these 'second-generation' adeno-of 293-Cre cells with lacZ-expressing FD-AdV plasmid DNA followed by infection by Bac-B4 at a MOI of 2000 p.f.u./ml resulted in rescue of the helper-free vector.…”

Section: Introductionmentioning

confidence: 99%

A novel system for the production of fully deleted adenovirus vectors that does not require helper adenovirus

et al. 2001

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Fully deleted adenovirus vectors (FD-AdVs) would appear to be promising tools for gene therapy. Since these vectors are deleted of all adenoviral genes, they require a helper adenovirus for their propagation. The contamination of the vector preparation by the helper limits the utility of currently existing FD-AdVs in gene therapy applications. We have developed an alternative system for the propagation of FD-AdVs, in which the adenoviral genes essential for replication and packaging of the vector are delivered into producer cells by a baculovirus-adenovirus hybrid. A hybrid baculovirus Bac-B4 was constructed to carry a Cre recombinase-excisable copy of the packaging-deficient adenovirus genome. Although the total size of the DNA insert in Bac-B4 was 38 kb, the genetic structure of this recombinant baculovirus was stable. Bac-B4 gave high yields in Sf9 insect cells, with titers of 5 × 10 8 p.f.u./ml before concentration. Transfection

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MHC class I-cestricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses

Cited by 597 publications

References 28 publications

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Inflammation and adaptive immune responses to adenoviral vectors injected into the brain: peculiarities, mechanisms, and consequences

A novel system for the production of fully deleted adenovirus vectors that does not require helper adenovirus

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