title: Early self-regulatory mechanisms control the magnitude of CD8+ T cell responses against liver stages of murine malaria.
abstract: Following immunization with Plasmodium yoelii sporozoites, the CD8(+) T cell population specific for the SYVPSAEQI epitope expressed in sporozoite and liver stages of this malaria parasite revealed the existence of a short term Ag presentation process that translated into a single clonal burst. Further expansion of this CD8(+) T cell population in conditions of sustained Ag exposure and additional supply of naive cells was inhibited by regulatory mechanisms that were developed as early as 24-48 h after priming. Studies using mouse models for Plasmodium or influenza virus infections revealed that this mechanism is Ag specific and is mediated by activated CD8(+) T cells that inhibit the priming of naive cells. This interference of the priming of naive cells appeared to result from limited access to Ag-presenting dendritic cells, which become disabled or are eliminated after contact with activated cells. Thus, concomitantly with the development of their effector antimicrobial capacity, CD8(+) T cells also acquire a self-regulatory role that is likely to represent one of the earliest mechanisms induced in the course of an immune response and that limits the magnitude of the early expansion of CD8(+) T lymphocytes reactive to microorganisms.
authors.affiliation: Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010, USA.
authors.forename: Julius C R
authors.initials: JC
authors.lastname: Hafalla
authors.forename: Alexandre
authors.initials: A
authors.lastname: Morrot
authors.forename: Gen-Ichiro
authors.initials: G
authors.lastname: Sano
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lafaille
authors.forename: Fidel
authors.initials: F
authors.lastname: Zavala
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000469:parasitology* / Q000637:transplantation; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells; D015536:Down-Regulation / Q000276:immunology; D007399:Interphase / Q000276:immunology; D008109:Liver Diseases, Parasitic / Q000276:immunology* / Q000469:parasitology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010967:Plasmodium yoelii / Q000254:growth & development / Q000276:immunology; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D034101:Sporozoites / Q000254:growth & development / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000469:parasitology / Q000637:transplantation; D014611:Vaccination
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan