The amalgam of naive CD4 + T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response.

Autor:	Even Z; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA., Meli AP; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA., Tyagi A; Yale Center for Genome Analysis, Yale School of Medicine, West Haven, CT 06516, USA., Vidyarthi A; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA., Briggs N; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Department of Internal Medicine (Infectious Diseases), Yale School of Medicine, New Haven, CT 06520, USA., de Kouchkovsky DA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA., Kong Y; Department of Biostatistics, Yale School of Public Health, New Haven, CT 06520, USA., Wang Y; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA., Waizman DA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA., Rice TA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA., De Kumar B; Yale Center for Genome Analysis, Yale School of Medicine, West Haven, CT 06516, USA., Wang X; Department of Genetics, Genomics and Informatics, University of Tennessee, Memphis, TN 38163, USA., Palm NW; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA., Craft J; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA., Basu MK; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA., Ghosh S; Department of Neurology, Yale School of Medicine, New Haven, CT 06520, USA; Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: sourav.ghosh@yale.edu., Rothlin CV; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: carla.rothlin@yale.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2024 Aug 13; Vol. 57 (8), pp. 1893-1907.e6. Date of Electronic Publication: 2024 Aug 02.
DOI:	10.1016/j.immuni.2024.07.006
Abstrakt:	Naive CD4 + T cells in specific pathogen-free (SPF) mice are characterized by transcriptional heterogeneity and subpopulations distinguished by the expression of quiescence, the extracellular matrix (ECM) and cytoskeleton, type I interferon (IFN-I) response, memory-like, and T cell receptor (TCR) activation genes. We demonstrate that this constitutive heterogeneity, including the presence of the IFN-I response cluster, is commensal independent insofar as being identical in germ-free and SPF mice. By contrast, Nippostrongylus brasiliensis infection altered this constitutive heterogeneity. Naive T cell-intrinsic transcriptional changes acquired during helminth infection correlated with and accounted for decreased immunization response to an unrelated antigen. These compositional and functional changes were dependent variables of helminth infection, as they disappeared at the established time point of its clearance in mice. Collectively, our results indicate that the naive T cell pool is subject to dynamic transcriptional changes in response to certain environmental cues, which in turn permutes the magnitude of the immune response. Competing Interests: Declaration of interests Z.E. is currently a medical student at the University of North Dakota; A.P.M. is a postdoctoral fellow at McGill University; D.A.d.K. is currently a resident at the University of California, San Diego; and Y.W. is currently a postdoctoral fellow at St. Jude Children’s Research Hospital. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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