Advisory Committee Chair
Chander Raman
Advisory Committee Members
Casey Weaver
James George
Scott Barnum
Louis Justement
Robert Kimberly
Document Type
Dissertation
Date of Award
2007
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
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 addi-tional 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, block-ing 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 func-tion 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 re-sistant to the development of EAE because the effector CD4 T-cells were unable to sur-vive 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 IFNγ 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 di- iii rect 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 dis-eases such as Multiple Sclerosis.
Recommended Citation
Axtell, Robert C., "The Role Of Cd5 In Experimental Autoimmune Encephalitomyelitis" (2007). All ETDs from UAB. 3659.
https://digitalcommons.library.uab.edu/etd-collection/3659