Inflammation durably imprints memory CD4+ T cells.

Autor:	Gray-Gaillard SL; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA., Solis S; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA., Chen HM; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA., Monteiro C; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA., Ciabattoni G; Department of Microbiology, New York University School of Medicine; New York, NY, USA., Samanovic MI; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA., Cornelius AR; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA., Williams T; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA., Geesey E; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA., Rodriguez M; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA., Ortigoza MB; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA., Ivanova EN; Department of Pathology, New York University School of Medicine; New York, NY, USA., Koralov SB; Department of Pathology, New York University School of Medicine; New York, NY, USA., Mulligan MJ; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA.; Department of Microbiology, New York University School of Medicine; New York, NY, USA., Herati RS; Department of Medicine, New York University Grossman School of Medicine; New York, NY, USA.; Department of Microbiology, New York University School of Medicine; New York, NY, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 May 22. Date of Electronic Publication: 2023 May 22.
DOI:	10.1101/2022.11.15.516351
Abstrakt:	Adaptive immune responses are induced by vaccination and infection, yet little is known about how CD4+ T cell memory differs when primed in these two contexts. Notably, viral infection is generally associated with higher levels of systemic inflammation than is vaccination. To assess whether the inflammatory milieu at the time of CD4+ T cell priming has long-term effects on memory, we compared Spike-specific memory CD4+ T cells in 22 individuals around the time of the participants' third SARS-CoV-2 mRNA vaccination, with stratification by whether the participants' first exposure to Spike was via virus or mRNA vaccine. Multimodal single-cell profiling of Spike-specific CD4+ T cells revealed 755 differentially expressed genes that distinguished infection- and vaccine-primed memory CD4+ T cells. Spike-specific CD4+ T cells from infection-primed individuals had strong enrichment for cytotoxicity and interferon signaling genes, whereas Spike-specific CD4+ T cells from vaccine-primed individuals were enriched for proliferative pathways by gene set enrichment analysis. Moreover, Spike-specific memory CD4+ T cells established by infection had distinct epigenetic landscapes driven by enrichment of IRF-family transcription factors, relative to T cells established by mRNA vaccination. This transcriptional imprint was minimally altered following subsequent mRNA vaccination or breakthrough infection, reflecting the strong bias induced by the inflammatory environment during initial memory differentiation. Together, these data suggest that the inflammatory context during CD4+ T cell priming is durably imprinted in the memory state at transcriptional and epigenetic levels, which has implications for personalization of vaccination based on prior infection history. Competing Interests: Declaration of Interests MJM reported potential competing interests: laboratory research and clinical trials contracts with Lilly, Pfizer (exclusive of the current work), and Sanofi for vaccines or MAB vs SARS-CoV-2; contract funding from USG/HHS/BARDA for research specimen characterization and repository; research grant funding from USG/HHS/NIH for SARS-CoV-2 vaccine and MAB clinical trials; personal fees from Meissa Vaccines, Inc. and Pfizer for Scientific Advisory Board service. RSH has received research support from CareDx for SARS-CoV-2 vaccine studies and has performed consulting work for Bristol-Myers-Squib.
Databáze:	MEDLINE
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