title: Distinct memory CD4+ T cells with commitment to T follicular helper- and T helper 1-cell lineages are generated after acute viral infection.
abstract: CD4(+) T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for long-lived antibody responses. However, it remains unclear whether there are CD4(+) memory T cells committed to the Tfh cell lineage after antigen clearance. By using adoptive transfer of antigen-specific memory CD4(+) T cell subpopulations in the lymphocytic choriomeningitis virus infection model, we found that there are distinct memory CD4(+) T cell populations with commitment to either Tfh- or Th1-cell lineages. Our conclusions are based on gene expression profiles, epigenetic studies, and phenotypic and functional analyses. Our findings indicate that CD4(+) memory T cells "remember" their previous effector lineage after antigen clearance, being poised to reacquire their lineage-specific effector functions upon antigen reencounter. These findings have important implications for rational vaccine design, where improving the generation and engagement of memory Tfh cells could be used to enhance vaccine-induced protective immunity.
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: J Scott
authors.initials: JS
authors.lastname: Hale
authors.forename: Ben
authors.initials: B
authors.lastname: Youngblood
authors.forename: Donald R
authors.initials: DR
authors.lastname: Latner
authors.forename: Ata Ur Rasheed
authors.initials: AU
authors.lastname: Mohammed
authors.forename: Lilin
authors.initials: L
authors.lastname: Ye
authors.forename: Rama S
authors.initials: RS
authors.lastname: Akondy
authors.forename: Tuoqi
authors.initials: T
authors.lastname: Wu
authors.forename: Smita S
authors.initials: SS
authors.lastname: Iyer
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D019175:DNA Methylation / Q000276:immunology; D044127:Epigenesis, Genetic / Q000276:immunology; D053804:Granzymes / Q000235:genetics; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054380:Receptors, CXCR5 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D059467:Transcriptome
chemical_list: D000956:Antigens, Viral; C513179:CXCR5 protein, mouse; D054380:Receptors, CXCR5; D053804:Granzymes