MAdCAM-1 Costimulates T Cells Through Integrin Alpha4/Beta7 to Cause Gene Expression Events Resembling Costimulation Through CD28

After revealing no effect of vedolizumab upon T cell density in colon biopsies, we demonstrate that MAdCAM-1 delivers a costimulatory signal comparable to that of CD28 in T cells both functionally and at the gene expression level, with only subtle differences identified in the latter concerning cytokines involved in pyogenic inflammation. Overall design: 102 T-cell samples were profiled using RNA-seq. PBMC from three donors were stimulated with each of four conditions ((1) OKT3 (anti-CD3) + human IgG (2) OKT3 + MAdCAM-1 (3) OKT3 + MAdCAM-1+ vedolizumab (4) OKT3 + anti-CD28) and samples were collected at five timepoints( 0, 0.5, 2, 6, and 24) following stimulation. From each donor, condition, and timepoint, 1000 CD4 and 1000 CD8 T-cells were sorted and sequenced.