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Activation and function of effector ...

Odegard, Jared M.

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Activation and function of effector CD4 T cells in systematic autoimmunity.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Activation and function of effector CD4 T cells in systematic autoimmunity./
作者:	Odegard, Jared M.
面頁冊數:	185 p.
附註:	Adviser: Joseph E. Craft.
Contained By:	Dissertation Abstracts International68-06B.
標題:	Health Sciences, Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3267334
ISBN:	9780549068709

Activation and function of effector CD4 T cells in systematic autoimmunity.
Odegard, Jared M.

Activation and function of effector CD4 T cells in systematic autoimmunity. - 185 p.

Adviser: Joseph E. Craft.

Thesis (Ph.D.)--Yale University, 2007.

CD4 T cells play an essential role in the production of autoantibodies in the MRLlpr mouse model of systemic lupus erythematosus. Neither the genetic mechanisms that permit the T cell response to self antigens, nor the precise mode of action of T cells in autoantibody production are well defined. We have first revisited the role of antigen hyper-responsiveness as a contributing factor to the loss of T cell self tolerance in MRL. Fas+/+ animals, and under in vivo conditions of immunization and lymphopenia, we find no evidence for a proliferative defect intrinsic to MRL T cells. Second, while the recent description of the follicular helper T cell subset has shed light on the specialized helper functions that occur in the germinal center, we have limited knowledge of the mechanisms of T cell help in the extrafollicular response, which is the dominant pathway of autoreactive B cell activation in the MRLlpr mouse. We show that a genetic disruption in the T cell molecule inducible costimulator (ICOS) leads to a severe defect in extrafollicular differentiation of IgG+ plasma cells without affecting B cell entry into the plasmablast pool. This plasma cell defect leads to a reduction in circulating IgG autoantibodies and reduction in the severity of glomerulonephritis. Corresponding with the defect in extrafollicular class switching, CD4 T cells require ICOS for IL-21 secretion and optimal B helper function as well as expression of CXCR4, but not CXCR5. These defects can be collectively ascribed to the selective loss of a novel subset of helper T cells marked by loss of the surface glycoprotein PSGL-1. PSGL-1lo T cells are unique in their expression of CXCR4 and capacity to promote IgG production in an IL-21 dependent manner. We present histological evidence for helper T cells in the extrafollicular focus and show their PSGL-1lo phenotype. Thus, our findings define an anatomically and functionally distinct effector T cell subset, which we term extrafollicular helper T cells (THEF), that play an important role in systemic autoimmunity and may also contribute to other extrafollicular antibody responses.

ISBN: 9780549068709Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Activation and function of effector CD4 T cells in systematic autoimmunity.
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