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Tracking B and T lymphocytes in vivo...

Litzinger, Mary.

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Tracking B and T lymphocytes in vivo during peptide-IgG gene-transferred tolerance induction.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Tracking B and T lymphocytes in vivo during peptide-IgG gene-transferred tolerance induction./
Author:	Litzinger, Mary.
Description:	127 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-09, Section: B, page: 4498.
Contained By:	Dissertation Abstracts International65-09B.
Subject:	Health Sciences, Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3147998
ISBN:	0496063588

Tracking B and T lymphocytes in vivo during peptide-IgG gene-transferred tolerance induction.
Litzinger, Mary.

Tracking B and T lymphocytes in vivo during peptide-IgG gene-transferred tolerance induction. - 127 p.

Source: Dissertation Abstracts International, Volume: 65-09, Section: B, page: 4498.

Thesis (Ph.D.)--The George Washington University, 2004.

IgG fusion proteins, delivered via retroviral gene therapy for B-cell antigen presentation, are tolerogenic for the epitopes associated with the IgG. Previous evidence suggests the importance of B cells and MHC class II presentation in tolerance induction. The overarching goal of this dissertation is to further clarify the mechanisms of action of this therapy.

ISBN: 0496063588Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Tracking B and T lymphocytes in vivo during peptide-IgG gene-transferred tolerance induction.
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100 1 $a Litzinger, Mary. $3 1900866
245 1 0 $a Tracking B and T lymphocytes in vivo during peptide-IgG gene-transferred tolerance induction.
300 $a 127 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-09, Section: B, page: 4498.
500 $a Director: David W. Scott.
502 $a Thesis (Ph.D.)--The George Washington University, 2004.
520 $a IgG fusion proteins, delivered via retroviral gene therapy for B-cell antigen presentation, are tolerogenic for the epitopes associated with the IgG. Previous evidence suggests the importance of B cells and MHC class II presentation in tolerance induction. The overarching goal of this dissertation is to further clarify the mechanisms of action of this therapy.
520 $a The dye USE was utilized to track the tolerogenic B cells in vivo. CFSE-labeled, retrovirally-transduced B-cell blasts primarily tracked to spleen, where they persisted for at least 60 days. Further, by day 7 post-injection, upwards of 95 percent had divided at least once. As non-transduced, LPS-stimulated B cells divided similarly, the division of the transduced B cells was likely a continued effect of LPS stimulation. The transduced B cells did not appear to express FasL nor did they kill Fas-expressing Jurkat cells in vitro. Pre-injection, the transduced B-cell blasts displayed upregulation of both B7 costimulatory molecules, and B7.2 upregulation was maintained through day 7 in vivo. Suggestive of a role of B7 in tolerance induction, transduced B cells from B7 knockout donors were not tolerogenic. These data suggest that tolerance is induced by B7 negative regulatory signaling, perhaps via CTLA-4, but tolerance is maintained by a lack of signal 2 since expression of B7 is lost in vivo.
520 $a CFSE similarly was utilized to track transgenic T cells specific for a processed ovalbumin peptide (DO11.10 T cells) in vivo during tolerance induction by OVA-IgG gene therapy. DO1 1.10 T cells did not divide or express early activation markers in response to our tolerogenic stimulus, OVA-IgG B cells, whereas the T cells responded to an immunization protocol. DO11.10 T cells comparably proliferated and upregulated activation markers in response to OVA footpad immunization in animals treated with OVA-IgG B cells and in those treated with control B cells. Nonetheless, animals treated with OVA-IgG gene therapy showed a significantly lower T-cell response to OVA in vitro following a boost, suggestive of tolerance. These data suggest that the antigen-specific T cells are tolerized in a 'stepwise' manner, susceptible to additional tolerizing signals upon exposure to a higher or added dose of antigen.
590 $a School code: 0075.
650 4 $a Health Sciences, Immunology. $3 1017716
650 4 $a Biology, Molecular. $3 1017719
690 $a 0982
690 $a 0307
710 2 0 $a The George Washington University. $3 1017405
773 0 $t Dissertation Abstracts International $g 65-09B.
790 1 0 $a Scott, David W., $e advisor
790 $a 0075
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3147998