Ctla-4’S Role In The Dysregulation Of T-Cell Function In Sarcoidosis

Rebecca Wang

School Name

Governor's School for Science and Math

Grade Level

12th Grade

Presentation Topic

Cell and Molecular Biology

Presentation Type

Mentored

Mentor

Mentor: Dr. Drake; Infectious Diseases Department, Vanderbilt University

Abstract

Sarcoidosis is an autoimmune disease with an unknown cause. In Sarcoidosis, the T-cells are activated to destroy harmful substances, but then do not deactivate and subside. The result is the formation of lumps, or granulomas, in the organs of the body, most commonly in the lungs and lymph glands in the chest. There is no cure; however drug treatment is often used to reduce inflammation. CTLA-4 is a glycoprotein of the Ig superfamily that acts as an immune checkpoint which regulates T-cell activation in T-cell-dependent immune responses. CTLA-4 signals lead to the down regulation of T-cell proliferation and activation. Since Sarcoidosis is caused by T-cells being activated and then staying activated, and CTLA-4 is an inhibitor of this activation, CTLA-4 can interfere with TCR-derived signals and block early signaling events. Finding a way to enhance the effects of CTLA-4 could potentially stop cell proliferation so the T-cells do not stay activated. However, researchers do not know which interactions or regions of CTLA-4 need to be targeted in order to enhance CTLA-4’s inhibitory functions. In this experiment, CD4+ and CD8+ T-cells taken from Sarcoidosis cells and controls were isolated. cDNA synthesis, using iScript, was conducted and Real-Time PCR was set up to target CTLA-4. It was found that there is a decreased CTLA-4 expression in Sarcoidosis that trends toward significance and a higher CTLA-4 expression in Sarcoidosis CD4 vs. CD8 T-cells. Even though the results showed no statistical significance, they were trending towards significance.

Location

Owens 202

Start Date

4-16-2016 9:30 AM

COinS
 
Apr 16th, 9:30 AM

Ctla-4’S Role In The Dysregulation Of T-Cell Function In Sarcoidosis

Owens 202

Sarcoidosis is an autoimmune disease with an unknown cause. In Sarcoidosis, the T-cells are activated to destroy harmful substances, but then do not deactivate and subside. The result is the formation of lumps, or granulomas, in the organs of the body, most commonly in the lungs and lymph glands in the chest. There is no cure; however drug treatment is often used to reduce inflammation. CTLA-4 is a glycoprotein of the Ig superfamily that acts as an immune checkpoint which regulates T-cell activation in T-cell-dependent immune responses. CTLA-4 signals lead to the down regulation of T-cell proliferation and activation. Since Sarcoidosis is caused by T-cells being activated and then staying activated, and CTLA-4 is an inhibitor of this activation, CTLA-4 can interfere with TCR-derived signals and block early signaling events. Finding a way to enhance the effects of CTLA-4 could potentially stop cell proliferation so the T-cells do not stay activated. However, researchers do not know which interactions or regions of CTLA-4 need to be targeted in order to enhance CTLA-4’s inhibitory functions. In this experiment, CD4+ and CD8+ T-cells taken from Sarcoidosis cells and controls were isolated. cDNA synthesis, using iScript, was conducted and Real-Time PCR was set up to target CTLA-4. It was found that there is a decreased CTLA-4 expression in Sarcoidosis that trends toward significance and a higher CTLA-4 expression in Sarcoidosis CD4 vs. CD8 T-cells. Even though the results showed no statistical significance, they were trending towards significance.