Spatiotemporal single-cell profiling of gastrointestinal GVHD reveals invasive and tissue-resident memory T cell states

One of the major barriers to understanding the control of T cell infiltration into target tissues has been the inherent difficulty in capturing the key variable of time in this process. Time is a critical variable, given that T cells are actively homing towards and infiltrating into target organs, and are concordantly evolving a highly pathogenic transcriptional program. Without understanding the time-dependency of T cell infiltration, we cannot fully comprehend key drivers and their dynamics. Here, we have been able to deconvolute time as a variable during T cell infiltration and tissue destruction during primate aGVHD by applying Serial Intravascular Staining ('SIVS') and pairing this with multiparameter flow cytotmetric and single-cell transcriptomic analysis. We also demonstrate significant overlap between NHP transcriptional signatures and those found in patients with active aGVHD, underscoring the clinical relevance of these findings. Overall design: Bulk RNA-Seq examination of transcriptomes of patient samples receiving placebo from the ABA2 clinical trial (NCT01743131).