title: Continuous Effector CD8(+) T Cell Production in a Controlled Persistent Infection Is Sustained by a Proliferative Intermediate Population.
abstract: Highly functional CD8(+) effector T (Teff) cells can persist in large numbers during controlled persistent infections, as exemplified by rare HIV-infected individuals who control the virus. Here we examined the cellular mechanisms that maintain ongoing T effector responses using a mouse model for persistent Toxoplasma gondii infection. In mice expressing the protective MHC-I molecule, H-2L(d), a dominant T effector response against a single parasite antigen was maintained without a contraction phase, correlating with ongoing presentation of the dominant antigen. Large numbers of short-lived Teff cells were continuously produced via a proliferative, antigen-dependent intermediate (Tint) population with a memory-effector hybrid phenotype. During an acute, resolved infection, decreasing antigen load correlated with a sharp drop in the Tint cell population and subsequent loss of the ongoing effector response. Vaccination approaches aimed at the development of Tint populations might prove effective against pathogens that lead to chronic infection.
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA. Electronic address: hamletchu.berkeley@gmail.com.
authors.forename: H Hamlet
authors.initials: HH
authors.lastname: Chu
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Shiao-Wei
authors.initials: SW
authors.lastname: Chan
authors.affiliation: Departments of Statistics, School of Mathematics, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: John Paul
authors.initials: JP
authors.lastname: Gosling
authors.affiliation: Center of Pathophysiology of Toulouse-Purpan, INSERM UMR1043-CNRS UMR5282, University of Toulouse, 31024 Toulouse Cedex 3, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchard
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Tsitsiklis
authors.affiliation: Applied Mathematics, School of Mathematics, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Grant
authors.initials: G
authors.lastname: Lythe
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
authors.affiliation: Applied Mathematics, School of Mathematics, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Carmen
authors.initials: C
authors.lastname: Molina-París
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA. Electronic address: erobey@berkeley.edu.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Robey
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell