Authors:

Sonali Vijay

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Type 1 Diabetes is an autoimmune disease in which the body's T lymphocytes erroneously attack insulin-producing pancreatic β-cells. Existing therapies for T1D, such as Abatacept an d other CTLA-4 inhibitors, have shown promise by reducing T cell activation and delaying disea se progression in phase II clinical trials. Additionally, the CD226 gene has been identified as harboring risk variants linked to T1D and other autoimmune disorders. TIGIT-Ig is a promising novel therapeutic agent with potential applications in T1D immunothe rapy, leveraging its immunosuppressive effects on T cell activation by augmenting T cell co-inhi bitory signaling and outcompeting pro-inflammatory, co-stimulatory signaling mediated b y CD226 Prior studies have established that TIGIT is involved in regulating T cell activity, but its specific effects on different T cell subsets in the context of autoimmune diseases like T 1D remain unclear. Here, we show that TIGIT-Ig selectively suppresses T cell activation in C D4+ memory T cells, in an antigen-specific manner.. In this study, we analyzed CD155/CD112 ex pression on T cell memory subsets and the impact of TIGT-Ig on T cell activation markers in splenocytes and CD3-enriched T cell populations from 8–10-week-old NOD mice. Compar ed to naïve T cells, memory T cells exhibited higher CD155 andCD112 expression, suggesting that TIGIT-Ig may preferentially impact effector T cells while maintaining naïve T cell func tion. Following TIGIT-Ig treatment, CD4+ and CD8+ T cells showed reduced CD25, CD44, CD69, and CD226 expression, indicating decreased activation in the presence of antigen-pre senting cells. In APC-free cultures, TIGIT-Ig treatment reduced activation in CD4+ T ce lls but not CD8+ T cells, highlighting its selective suppressive effects on T cell subsets. Overall , our data suggests that TIGIT-Ig provides a more targeted approach than other immunothera pies by bolstering T cell co-inhibitory signaling as an immune modulator, with implications for the prevention or suspension of T1D.

Source:

University of Florida / Sonali Vijay, Matthew Brown, Emerson Parks, Kyle Madrid, Rachel / 2024

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Co-authors:

Sonali Vijay