Low-dose Interleukin-2 After Myocardial Infarction to Investigate Effects on Tissue-resident Regulatory T Cells

Overview

The primary goals of this study are to compare the differences in tissue-resident Treg gene signature for activation, proliferation, and suppressive function using single-cell/-nucleus RNA sequencing in patients treated with ld-IL-2 compared to control grouped by individual tissue beds from in and around the heart. Additionally, tissue-resident Tregs will be compared to peripheral blood Tregs from the same patient to assess the differential effect of ld-IL-2 on the two compartments.

So far, our lab has looked at Tregs and immune cells in the blood. The question remained whether ld-IL-2 can have the desired effect on Tregs in tissues, particularly the vasculature and cardiac tissues, where they could promote tissue repair and potentially improve clinical outcomes for patients after a myocardial infarction which causes significant tissue damage. Clinically, this could lead to lower rates of heart failure. In both the LILACS and IVORY trials, the effect measured was on circulating Tregs, whilst the effect of ld-IL-2 on tissue resident immune cells remains unknown. Therefore, the aims of the study are to understand the effect of treatment with ld-IL-2 on tissue-resident immune cells in the context of ischaemic heart disease and acute MI where there has been acute tissue damage. This includes: 1. Assessment if ld-IL-2, given systemically to patients at our proposed doses, can alter Tregs in the vasculature and cardiac tissues to exhibit a tissue repair and anti-inflammatory phenotype 2. Studying the relationship between the vasculature, cardiac tissues and circulating immune cells after systemic ld-IL-2 administration.