Dissertation/Thesis Abstract

The role of CD5 in experimental autoimmune encephalitomyelitis
by Axtell, Robert C., Ph.D., The University of Alabama at Birmingham, 2007, 95; 3286365
Abstract (Summary)

The regulation of activation, differentiation and persistence of effector T-cells are critical for the development of Experimental Autoimmune Encephalomyelitis (EAE), the animal model of Multiple Sclerosis. Until now, the function of CD5 was accepted to be a negative regulator of T-cell activation. This dissertation reports that CD5 has an additional role in T-cell responses, which is to promote cell survival. Observations from EAE experiments revealed that mice deficient in CD5 exhibited decreased disease severity which was associated with the inability of activated T-cells to survive. Moreover, blocking the engagement of CD5 in mice led to enhanced activation induced cell death (AICD) and this protected the mice from EAE. These results demonstrate that signaling through CD5 engagement plays a key role in regulating T-cell survival. This pro-survival function of CD5 is transduced through the activation of the serine/threonine kinase, CK2, which is associated with this receptor. Mice lacking CD5-CK2 signaling were highly resistant to the development of EAE because the effector CD4 T-cells were unable to survive at the site of inflammation. Further characterization of effector cells in the spinal cords of these mice revealed that the resistance to disease was associated with a striking decrease in a population of TH cells that co-expresses both IFN╬│ and IL-17. In addition, T-cells from CD5-CK2 signaling deficient mice were hyper-proliferative to a primary stimulation, but following restimulation, they rapidly developed non-responsiveness and exhibited elevated AICD. These results indicate that the CD5-CK2 pathway plays a direct role in the activation and in the persistence of effector T-cells in a neuro-inflammatory disease; this may be a potential target for the treatment of autoimmune diseases such as Multiple Sclerosis.

Indexing (document details)
Advisor: Raman, Chander
Commitee:
School: The University of Alabama at Birmingham
School Location: United States -- Alabama
Source: DAI-B 68/10, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Immunology
Keywords: Autoimmunity, Experimental autoimmune encephalomyelitis, Multiple sclerosis, T cell survival, T cells
Publication Number: 3286365
ISBN: 9780549288640
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