Fall Research Expo 2020

Differences in T Cell Subset Frequencies in Canine Myasthenia Gravis Patients

Myasthenia gravis is a T cell-dependent B cell-mediated autoimmune disease that causes autoantibodies to attack the acetylcholine receptors at the neuromuscular junction. Over time, this lack of stimulation of the muscle cell results in degeneration and muscle weakness. T lymphocytes are a critical part of the immune system in determining the immune response; T regulatory cells have suppressive functions that help to prevent autoimmune diseases. This study aimed to explore the relationship of T lymphocyte population identities and frequencies and Treg frequency and activation between healthy and myasthenia gravis canine patients. We theorized that dogs with myasthenia gravis may have decreased frequencies of these cells, resulting in increased susceptibility to autoimmune diseases. Blood samples collected by Ying Wu in Dr. Oliver Garden’s lab were analyzed using a data analysis program called FlowJo so as to compare the frequency and characteristics of T cells in healthy and diseased dogs. 

This research concluded that T lymphocyte and T regulatory frequencies do not differ between healthy and diseased dogs. However, the frequencies of these cells in dogs that recover from myasthenia gravis increase over the course of their disease, trending towards the average frequency of healthy dogs. Interestingly, this research suggested that the ratio of CD4+ helper to CD8+ cytotoxic T cells is significantly increased in myasthenia gravis patients. Further research needs to be conducted so as to explore the change in T cell frequency and identity over the course of recovery.

 

PRESENTED BY
PURM - Penn Undergraduate Research Mentoring Program
College of Arts & Sciences 2023
Advised By
Jennifer Punt
Dr.
Join Carly for a virtual discussion
PRESENTED BY
PURM - Penn Undergraduate Research Mentoring Program
College of Arts & Sciences 2023
Advised By
Jennifer Punt
Dr.

Comments

Hi Carly! I found your research really interesting. Here are a couple questions I have: How does canine myasthenia gravis differ diagnostically and symptomatically from the same disease in other species? Is the research you have conducted on canine myasthenia gravis applicable to myasthenia gravis in other species? If you were to hypothesize the biological reason for a higher CD4+/CD8+ T cell ratio as well as T cell and Treg cell frequency change over disease course, what would your rationale be?

Hello Carly! I found your research to be very stimulating. I am a big dog lover. I have some questions: because of your small cohort size, do you think that you can confidently confirm your conclusions that T lymphocytes and Treg frequencies do not differ between healthy and sick dogs? Also, since you used FoxP3 to identify T regulatory cells, why did you also use it to test how activated they are? Overall, great work!

Hello Carly! I found your research to be very stimulating. I am a big dog lover. I have some questions: because of your small cohort size, do you think that you can confidently confirm your conclusions that T lymphocytes and Treg frequencies do not differ between healthy and sick dogs? Also, since you used FoxP3 to identify T regulatory cells, why did you also use it to test how activated they are? Overall, great work!

Hello Carly! I found your research to be very stimulating. I am a big dog lover. I have some questions: because of your small cohort size, do you think that you can confidently confirm your conclusions that T lymphocytes and Treg frequencies do not differ between healthy and sick dogs? Also, since you used FoxP3 to identify T regulatory cells, why did you also use it to test how activated they are? Overall, great work!

Hello Carly! I found your research to be very stimulating. I am a big dog lover. I have some questions: because of your small cohort size, do you think that you can confidently confirm your conclusions that T lymphocytes and Treg frequencies do not differ between healthy and sick dogs? Also, since you used FoxP3 to identify T regulatory cells, why did you also use it to test how activated they are? Overall, great work!

A wonderful poster, Carly - and a wonderful analysis.  You will be acknowledged on Julia's paper for your work with the FoxP3+ cells (kudos).  These questions are good - and I know you can answer them well.  As you know, your data hints at an intriguing difference in FoxP3+ cell frequencies!  Statistical significance in one thing - and trends are another.  More experiments to do!

 

Congrats, Carly!!! This is fascinating research and a beautiful poster! I was just wondering what role the CD4:CD8 T cell ratio played in your research/what implications this would have for the dogs with myasthenia gravis?

I'm so glad we got to meet and work together this summer!

Carly, 

Your poster is absolutely beautiful and incredibly clear/informative. I know that intravenous immunoglobulin (IVIg) is a pretty common immunotherapeutic approach to treat patients with Myasthenia gravis -- do you have any idea how dogs with this disease are treated? I believe that IVIg is quite expensive so I would be surprised if it is commonly administered to dogs. 

Anyways, well done!

(PS Jenni Punt is SO awesome)

 

 

Carly, this research is incredible! I was wondering if during the research you recorded the different frequencies T lymphocyte and T regulatory during different stages of the diseases, and if that is pertinent at all to your research?