title: High initial frequency of TCR-transgenic CD8 T cells alters inflammation and pathogen clearance without affecting memory T cell function.
abstract: In adoptive transfer experiments, the initial frequency of naïve TCR-transgenic T cells impacts CD8 T cell phenotype after acute infections. The exact reasons for the observed changes, however, are unclear and it is unknown whether alterations in phenotype translate into impaired memory T cell function as well. Here we perform in vivo comparisons of effector and memory CD8 T cells generated from high or low numbers of naïve precursors. We show that high numbers of adoptively transferred T cells exhibit effector functions that alter systemic inflammation and pathogen abundance in the initial days after infection. While these altered environmental conditions resulted in profound changes in primary effector and memory CD8 T cell phenotype, memory T cells derived from both high and low numbers of naïve precursors protected equally well against re-infection and generated secondary effector and memory T cells that were similar in numbers and phenotype. Our results confirm the necessity to use low numbers of naïve precursors to mimic endogenous immune responses but show at the same time that memory CD8 T cell function in adoptive transfers is independent of input numbers.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Wirth
authors.forename: Nhat-Long L
authors.initials: NL
authors.lastname: Pham
authors.forename: John T
authors.initials: JT
authors.lastname: Harty
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Badovinac
mesh_terms: D019264:Adoptive Transfer / Q000379:methods* / Q000592:standards; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000637:transplantation*; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000628:therapy; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016176:T-Lymphocyte Subsets; D016896:Treatment Outcome
chemical_list: D011948:Receptors, Antigen, T-Cell