Aberrant T cell activation in the NOD mouse: A critical role for APCs in autoimmune disease.

Format:

Book

Thesis/Dissertation

Author/Creator:

Moore, Daniel Jensen.

Contributor:

University of Pennsylvania.

Language:

English

Subjects (All):

Cytology.

0379.

Local Subjects:

0379.

Physical Description:

152 pages

Contained In:

Dissertation Abstracts International 64-04B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

The many commonalities between the development of autoimmune diabetes in the NOD mouse and its development in patients with Type I Diabetes Mellitus have made this model a paradigm for the investigation of autoimmune disease. However, the NOD mouse is also susceptible to a panoply of other autoimmune disease manifestations suggesting that this murine system may model more than just diabetes. In Chapter III, we explore the possibility that the immune system of the NOD mouse may share features with other autoimmune prone murine strains. We demonstrate here that CD4 T cell hypoproliferation which has been extensively characterized in the NOD mouse also characterizes the MRL/MpJ and NZBxNZW models of lupus. In Chapter IV, we dissect this phenotype and determine that it is not intrinsic to the T cell compartment of these strains. Rather, it results from reliance on B cell mediated co-stimulation, a finding that implicates deficiencies in other professional APC compartments or altered B cell APC function in these diseases processes. In Chapter V, we utilize a chimeric system within the NOD background to discriminate among these possibilities. Our studies indicate that deficiencies within the compartments of professional APCs may be a crucial factor in the development of an immune system prone to autoimmune disease. In Chapter VI, we continue to explore the contribution of APC function to the establishment of tolerance. Studies here suggest that the B lymphocyte compartment may play a critical role in the induction of tolerance mediated by anti-CD45RB. The delicate contributions of APC function to the generation and maintenance of a tolerant state may underlie both the development of autoimmunity within the NOD mouse and its subsequent resistance to curative regimens designed to promote tolerance to grafted tissue.

Notes:

Source: Dissertation Abstracts International, Volume: 64-04, Section: B, page: 1585.

Supervisor: Ali Naji.

Thesis (Ph.D.)--University of Pennsylvania, 2003.

Local Notes:

School code: 0175.

ISBN:

9780496352104

Access Restriction:

Restricted for use by site license.