title: The control of CD8+ T cell responses is preserved in perforin-deficient mice and released by depletion of CD4+CD25+ regulatory T cells.
abstract: Immune suppression by Treg has been demonstrated in a number of models, but the mechanisms of this suppression are only partly understood. Recent work has suggested that Tregs may suppress by directly killing immune cell populations in vivo in a perforin- and granzyme B-dependent manner. To establish whether perforin is necessary for the regulation of immune responses in vivo, we examined OVA-specific CD8(+) T cell responses in WT and PKO mice immunized with OVA and α-GalCer and the expansion of WT OT-I CD8(+) T cells adoptively transferred into WT or PKO mice immunized with DC-OVA. We observed similar expansion, phenotype, and effector function of CD8(+) T cells in WT and PKO mice, suggesting that CD8(+) T cells were subjected to a similar amount of regulation in the two mouse strains. In addition, when WT and PKO mice were depleted of Tregs by anti-CD25 mAb treatment before DC-OVA immunization, CD8(+) T cell proliferation, cytotoxicity, and cytokine production were increased similarly, suggesting a comparable involvement of CD25(+) Tregs in controlling T cell proliferation and effector function in these two mouse strains. These data suggest that perforin expression is not required for normal immune regulation in these models of in vivo CD8(+) T cell responses induced by immunization with OVA and α-GalCer or DC-OVA.
authors.affiliation: 2.Entrance 7 Kelburn Parade, 6012 Kelburn, Wellington, New Zealand. fronchese@malaghan.org.nz.
authors.forename: Haley
authors.initials: H
authors.lastname: Ataera
authors.forename: Helen M A
authors.initials: HM
authors.lastname: Simkins
authors.forename: Evelyn
authors.initials: E
authors.lastname: Hyde
authors.forename: Jianping
authors.initials: J
authors.lastname: Yang
authors.forename: Ian F
authors.initials: IF
authors.lastname: Hermans
authors.forename: Troels R
authors.initials: TR
authors.lastname: Petersen
authors.forename: Franca
authors.initials: F
authors.lastname: Ronchese
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D003713:Dendritic Cells / Q000378:metabolism; D005699:Galactosylceramides / Q000378:metabolism; D007114:Immunization; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D037181:Lectins, C-Type; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins / Q000172:deficiency* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory
chemical_list: D005699:Galactosylceramides; D053645:Interleukin-2 Receptor alpha Subunit; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic; C493154:alpha-galactosylceramide; C483886:perforin, mouse; D010047:Ovalbumin
keywords: DC vaccines; cytokine production; killing; rodent