title: In vivo CD4+ T cell tolerance induction versus priming is independent of the rate and number of cell divisions.
abstract: In vitro studies have suggested that tolerance induction (i.e., anergy) is associated with an inability of T cells to proliferate vigorously upon Ag recognition. In vivo, the relationship between T cell proliferation and tolerance induction is less clear. To clarify this issue, we have been studying a model system in which naive CD4+ T cells specific for the model Ag hemagluttinin (HA) are adoptively transferred into different transgenic founder lines of mice expressing HA as a peripheral self-Ag. When transferred into two lines whose HA expression differs by at least 1000-fold, HA-specific T cells undergo multiple rounds of cell division before reaching a nonresponsive (i.e., tolerant) state. While the proliferative response is more rapid in mice expressing higher levels of HA, the T cells become tolerant regardless of the level of peripheral HA expression. When the T cells encounter HA expressed as a viral Ag, they proliferate at a similar rate and undergo the same number of divisions as with self-HA, but they do not become tolerant. These results indicate that a tolerizing stimulus can induce similar T cell mitotic rates as a priming stimulus. Therefore, CD4+ T cell tolerance induction in vivo is not the result of an insufficient proliferative response elicited upon TCR engagement.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. aadler@up.uchc.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Adler
authors.forename: C T
authors.initials: CT
authors.lastname: Huang
authors.forename: G S
authors.initials: GS
authors.lastname: Yochum
authors.forename: D W
authors.initials: DW
authors.lastname: Marsh
authors.forename: D M
authors.initials: DM
authors.lastname: Pardoll
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics; D002999:Clone Cells / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D007108:Immune Tolerance / Q000235:genetics; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus