title: Local Cellular and Cytokine Cues in the Spleen Regulate In Situ T Cell Receptor Affinity, Function, and Fate of CD8+T Cells.
abstract: T cells rapidly undergo contraction upon viral clearance, but how T cell function and fate are determined during this phase is unclear. During the contraction phase of an acute infection with lymphocytic choriomeningitis virus, we found that virus-specific CD8+T cells within the splenic red pulp (RP) had higher two-dimensional (2D) effective affinity than those within the white pulp (WP). This increased antigen recognition of RP-derived CD8+T cells correlated with more efficient target cell killing and improved control of viremia. FoxP3+regulatory T cells and cytokine TGF-β limited the 2D-affinity in the WP during the contraction phase. Anatomical location drove gene expression patterns in CD8+T cells that led to preferential differentiation of memory precursor WP T cells into long-term memory cells. These results highlight that intricate regulation of T cell function and fate is determined by anatomic compartmentalization during the early immune contraction phase.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30329, USA; Yerkes National Primate Research Center, Emory Vaccine Center, Atlanta, GA 30329, USA.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Seo
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Prithiviraj
authors.initials: P
authors.lastname: Jothikumar
authors.affiliation: Yerkes National Primate Research Center, Emory Vaccine Center, Atlanta, GA 30329, USA; Department of Pediatrics and Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30329, USA.
authors.forename: Mehul S
authors.initials: MS
authors.lastname: Suthar
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address: cheng.zhu@bme.gatech.edu.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30329, USA; Yerkes National Primate Research Center, Emory Vaccine Center, Atlanta, GA 30329, USA. Electronic address: arash.grakoui@emory.edu.
authors.forename: Arash
authors.initials: A
authors.lastname: Grakoui
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002469:Cell Separation; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D007156:Immunologic Memory / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D059467:Transcriptome
chemical_list: D016207:Cytokines; D011948:Receptors, Antigen, T-Cell
keywords: LCMV; T cell memory; T cell receptor; anti-viral CD8(+) T cell responses; immune contraction; peptide MHC interaction; red pulp; splenic compartments; white pulp