title: Protein vaccines induce uncommitted IL-2-secreting human and mouse CD4 T cells, whereas infections induce more IFN-gamma-secreting cells.
abstract: Mouse and human CD4 T cells primed during an immune response may differentiate into effector phenotypes such as Th1 (secreting IFN-gamma) or Th2 (secreting IL-4) that mediate effective immunity against different classes of pathogen. However, primed CD4 T cells can also remain uncommitted, secreting IL-2 and chemokines, but not IFN-gamma or IL-4. We now show that human CD4 T cells primed by protein vaccines mostly secreted IL-2, but not IFN-gamma, whereas in the same individuals most CD4 T cells initially primed by infection with live pathogens secreted IFN-gamma. We further demonstrate that many tetanus-specific IL-2+IFN-gamma- cells are uncommitted and that a single IL-2+IFN-gamma- cell can differentiate into Th1 or Th2 phenotypes following in vitro stimulation under appropriate polarizing conditions. In contrast, influenza-specific IL-2+IFN-gamma- CD4 cells maintained a Th1-like phenotype even under Th2-polarizing conditions. Similarly, adoptively transferred OTII transgenic mouse T cells secreted mainly IL-2 after priming with OVA in alum, but were biased toward IFN-gamma secretion when primed with the same OVA peptide presented as a pathogen Ag during live infection. Thus, protein subunit vaccines may prime a unique subset of differentiated, but uncommitted CD4 T cells that lack some of the functional properties of committed effectors induced by infection. This has implications for the design of more effective vaccines against pathogens requiring strong CD4 effector T cell responses.
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology, and Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Anagha A
authors.initials: AA
authors.lastname: Divekar
authors.forename: Dietmar M W
authors.initials: DM
authors.lastname: Zaiss
authors.forename: F Eun-Hyung
authors.initials: FE
authors.lastname: Lee
authors.forename: Dacheng
authors.initials: D
authors.lastname: Liu
authors.forename: David J
authors.initials: DJ
authors.lastname: Topham
authors.forename: Alice J A M
authors.initials: AJ
authors.lastname: Sijts
authors.forename: Tim R
authors.initials: TR
authors.lastname: Mosmann
mesh_terms: D000328:Adult; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000637:transplantation; D013745:Tetanus Toxoid / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control
chemical_list: D007376:Interleukin-2; D013745:Tetanus Toxoid; D022223:Vaccines, Subunit; D007371:Interferon-gamma