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Regulation of the cytotoxic and inte...

Snyder (Cappione), Jennifer Elizabeth.

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Regulation of the cytotoxic and interferon-gamma effector functions of CD8+ T cells.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Regulation of the cytotoxic and interferon-gamma effector functions of CD8+ T cells./
Author:	Snyder (Cappione), Jennifer Elizabeth.
Description:	180 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0048.
Contained By:	Dissertation Abstracts International66-01B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3161825
ISBN:	0496956841

Regulation of the cytotoxic and interferon-gamma effector functions of CD8+ T cells.
Snyder (Cappione), Jennifer Elizabeth.

Regulation of the cytotoxic and interferon-gamma effector functions of CD8+ T cells. - 180 p.

Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0048.

Thesis (Ph.D.)--University of Rochester, 2004.

CD8+ T cells are pivotal to the control of many infections, particularly viral. Two of the major effector functions of CD8+ T cells are the secretion of the cytokine IFN-gamma and the ability to lyse infected cells. IFN-gamma is able to directly inhibit viral replication within infected cells, and it also is a potent activator of macrophages and dendritic cells, two of the major cell types involved in phagocytosis of infectious particles and efficient presentation of foreign antigens to stimulate other cells of the immune system. The cytotoxic effector function of CD8 + T cells often leads to rapid elimination of the infection due to the death and degradation of an infected cell before the pathogen has the ability to effectively replicate.

ISBN: 0496956841Subjects--Topical Terms:

1017686
Biology, Cell.

Regulation of the cytotoxic and interferon-gamma effector functions of CD8+ T cells.
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100 1 $a Snyder (Cappione), Jennifer Elizabeth. $3 1905519
245 1 0 $a Regulation of the cytotoxic and interferon-gamma effector functions of CD8+ T cells.
300 $a 180 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0048.
500 $a Supervisor: Tim R. Mosmann.
502 $a Thesis (Ph.D.)--University of Rochester, 2004.
520 $a CD8+ T cells are pivotal to the control of many infections, particularly viral. Two of the major effector functions of CD8+ T cells are the secretion of the cytokine IFN-gamma and the ability to lyse infected cells. IFN-gamma is able to directly inhibit viral replication within infected cells, and it also is a potent activator of macrophages and dendritic cells, two of the major cell types involved in phagocytosis of infectious particles and efficient presentation of foreign antigens to stimulate other cells of the immune system. The cytotoxic effector function of CD8 + T cells often leads to rapid elimination of the infection due to the death and degradation of an infected cell before the pathogen has the ability to effectively replicate.
520 $a While there are excellent methods to evaluate both the amount of IFN-gamma secreted by a population of effector CD8+ T cells and the frequencies of CD8+ T cells secreting IFN-gamma, the assays to evaluate their cytotoxic function are not as informative. Therefore, a novel technique was developed, the Lysispot, which enabled a direct measurement of the frequencies of cytotoxic cells within a population of 'effector' cells, either in vitro or in vivo stimulated mouse or human cells. Combining the Lysispot assay with the IFN-gamma Elispot assay in two-color Elispot and Fluorispot assays, it was discovered that these two effector functions are independently regulated on a single cell level.
520 $a To investigate what factors may have the ability to control the selective expression of these two functions by individual CD8+ T cells, the Multiparameter Analysis Technique was employed. A homogenous population of activated CD8+ T cells were cultured with all possible combinations of as many as 8 different cytokines to evaluate whether exposure to particular cytokine combinations can alter the frequencies of CD8+ T cells exerting each of these two effector functions. It was found that cytokines could have dominant effects, or synergize with other cytokines, or antagonize others to alter the ratio of IFN-gamma secreting to cytotoxic cells. Also, several combinations of cytokines induced CD8 + T cells to express many characteristics of Resting Memory CD8 + T cells and Natural Killer cells found in vivo.
520 $a Finally, the Lysispot assay was performed on peripheral blood mononuclear cells from HIV infected patients. HIV peptide-specific cytotoxic cells were detectable directly ex vivo from infected patients; and the ratio of IFN-gamma to cytotoxic cells varied substantially between different peptide pools within an individual patient. Also, there was no significant difference between the IFN-gamma: CTL ratio amongst peptide pools specific for HIV, CMV or EBV within one patient. This Lysispot data raises questions about previous reports (using bulk cytotoxicity assays) of selective inhibition of ex vivo cytotoxicity specific for HIV peptides compared with peptide responses for other chronic viral infections.
590 $a School code: 0188.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Microbiology. $3 1017734
690 $a 0379
690 $a 0410
710 2 0 $a University of Rochester. $3 515736
773 0 $t Dissertation Abstracts International $g 66-01B.
790 1 0 $a Mosmann, Tim R., $e advisor
790 $a 0188
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3161825