Date of Award

Spring 5-22-2026

Document Type

Honors Project

University Scholars Director

Dr. Joshua Tom

First Advisor/Committee Member

Dr. John Douglass

Keywords

translational immunology, immunology, type 1 diabetes, flow cytometry

Abstract

Type 1 diabetes (T1D) is an autoimmune disease targeting the insulin-producing beta cells of the pancreas. The discovery of insulin revolutionized the treatment of T1D, but current research into T1D has progressed from disease management to possible prevention or delayed onset of diagnosis. One drug currently in use is teplizumab, an anti-CD3 monoclonal antibody that has been shown to delay the onset of T1D in some, but not all, at-risk individuals. High levels of a subset of peripheral blood CD8+ T cells we call SKIMs (stable KLRG1+ IL7Ra+ memory cells), which include MAIT (mucosal-associated invariant T) cells, have been associated with nonresponse to anti-CD3-mediated delay of T1D diagnosis. Here, we further explore these non-response associated CD8+ T cells in the context of vaccination, cancer, and non-diabetes autoimmune conditions to determine potential modulators. We analyzed flow cytometry data from separate studies of cancer patients and vaccination to quantify how populations of SKIMs change in response to various therapeutics. We also designed a flow cytometry panel to ask if drugs targeting receptors expressed on MAITs would impact the frequency of MAITs and SKIMs. This could inform us of similarities in the biology of these cell populations. The results suggest an anti-PD1 cancer therapeutic, pembrolizumab, inhibits SKIMs while flu vaccination has no effect, suggesting that PD-1 engagement, but not inflammation associated with viral infection, modulates SKIM levels. The results of the flow cytometry panel examining the effect of therapeutics predicted to decrease MAITs do not show a strong effect on either MAITs or SKIMs, though there are some nonsignificant visual trends. Together, identifying modulators of SKIMs will enable understanding of how this unique CD8+T cell subset contributes to non-response to anti-CD3 and could lead to more personalized medicine for T1D.

Comments

A project submitted in partial fulfillment of the requirements of the University Scholars Honors Program.

Copyright Status

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Additional Rights Information

Copyright held by author.

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