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Granzyme expression and function in ...

Cai, Sheng Feng.

Granzyme expression and function in effector and regulatory T cells.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Granzyme expression and function in effector and regulatory T cells.
Author:	Cai, Sheng Feng.
Description:	173 p.
Notes:	Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: 2014.
Notes:	Adviser: Timothy Ley.
Contained By:	Dissertation Abstracts International72-04B.
Subject:	Health Sciences, Immunology.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3443349
ISBN:	9781124481326

Granzyme expression and function in effector and regulatory T cells.
Cai, Sheng Feng.

Granzyme expression and function in effector and regulatory T cells. - 173 p.

Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: 2014.

Thesis (Ph.D.)--Washington University in St. Louis, 2011.

The perforin/granzyme pathway is a central component of anti-tumor and antiviral effector immune responses mediated by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. However, little is known about the conditions under which granzymes, in particular granzyme C, is expressed in discrete T and NK cell subsets. Thus, we generated a granzyme C-specific monoclonal antibody and used flow cytometry to characterize its expression at single-cell resolution in lymphocytes that were derived from either wild-type mice or granzyme B-deficient mice that have a small deletion within the proximal portion of the granzyme B gene. These studies revealed that deletion of this region perturbs granzyme expression, which results in earlier and more abundant expression of granzyme C in both T and NK cells, suggesting that regulatory elements within the deleted region are important for controlling the expression of granzyme C.

ISBN: 9781124481326Subjects--Topical Terms:

226966
Health Sciences, Immunology.

Granzyme expression and function in effector and regulatory T cells.
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100 1 $a Cai, Sheng Feng. $3 530973
245 1 0 $a Granzyme expression and function in effector and regulatory T cells.
300 $a 173 p.
500 $a Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: 2014.
500 $a Adviser: Timothy Ley.
502 $a Thesis (Ph.D.)--Washington University in St. Louis, 2011.
520 $a The perforin/granzyme pathway is a central component of anti-tumor and antiviral effector immune responses mediated by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. However, little is known about the conditions under which granzymes, in particular granzyme C, is expressed in discrete T and NK cell subsets. Thus, we generated a granzyme C-specific monoclonal antibody and used flow cytometry to characterize its expression at single-cell resolution in lymphocytes that were derived from either wild-type mice or granzyme B-deficient mice that have a small deletion within the proximal portion of the granzyme B gene. These studies revealed that deletion of this region perturbs granzyme expression, which results in earlier and more abundant expression of granzyme C in both T and NK cells, suggesting that regulatory elements within the deleted region are important for controlling the expression of granzyme C.
520 $a In addition to effector lymphocytes, we previously demonstrated that granzymes are expressed in in vitro-activated human and tumor-activated murine regulatory T (Treg) cells. Although no granzyme C was detected in murine Treg cells, we observed granzyme B expression in T reg cells alloactivated in mixed lymphocyte reactions, in a model of graft-versus-host disease (GvHD), and in an allogeneic tumor challenge model. However, wild-type and granzyme B-deficient Treg cells were equally able to suppress effector T (Teff) cell proliferation driven by multiple stimuli, including allogeneic antigen-presenting cells. Adoptive transfer of granzyme B-deficient Treg cells prevented GvHD lethality and suppressed GvHD-associated serum cytokine production in vivo. These data suggesting that granzyme B is not required for Treg cell function in the setting of allogeneic mismatch are in contrast with our previous findings demonstrating that granzyme B plays a non-redundant role in Treg cell-mediated suppression of anti-tumor responses. Gene expression profiling of purified Treg cells revealed broad changes in the molecular signatures of naive, tumor-activated, and GvHD-activated Treg cells, suggesting that cell-intrinsic differences during Treg cell activation may partially account for the differential phenotypes observed in these models. Finally, these findings also suggest that targeting discrete Treg cell suppressive mechanisms may be therapeutically beneficial in segregating GvHD and graft-versus-tumor immune responses.
590 $a School code: 0252.
650 4 $a Health Sciences, Immunology. $3 226966
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710 2 $a Washington University in St. Louis. $b Biology & Biomedical Sciences (Immunology). $3 530974
773 0 $t Dissertation Abstracts International $g 72-04B.
790 1 0 $a Ley, Timothy, $e advisor
790 1 0 $a Atkinson, John P. $e committee member
790 1 0 $a Colonna, Marco $e committee member
790 1 0 $a Hansen, Ted H. $e committee member
790 1 0 $a Hsieh, Chyi-Song $e committee member
790 1 0 $a Russell, John H. $e committee member
790 $a 0252
791 $a Ph.D.
792 $a 2011
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3443349