title: Protein kinase C η is required for T cell activation and homeostatic proliferation.
abstract: Protein kinase C η (PKCη) is abundant in T cells and is recruited to the immunological synapse that is formed between a T cell and an antigen-presenting cell; however, its function in T cells is unknown. We showed that PKCη was required for the activation of mature CD8+ T cells through the T cell receptor. Compared with wild-type T cells, PKCη-/- T cells showed poor proliferation in response to antigen stimulation, a trait shared with T cells deficient in PKCθ, which is the most abundant PKC isoform in T cells and was thought to be the only PKC isoform with a specific role in T cell activation. In contrast, only PKCη-deficient T cells showed defective homeostatic proliferation, which requires self-antigen recognition. PKCη was dispensable for thymocyte development; however, thymocytes from mice doubly deficient in PKCη and PKCθ exhibited poor development, indicating some redundancy between the PKC isoforms. Deficiency in PKCη or PKCθ had opposing effects on the relative numbers of CD4+ and CD8+ T cells. PKCη-/- mice had a higher ratio of CD4+ to CD8+ T cells compared to that of wild-type mice, whereas PKCθ-/- mice had a lower ratio. Mice deficient in both isoforms exhibited normal cell ratios. Together, these data suggest that PKCη shares some redundant roles with PKCθ in T cell biology and also performs nonredundant functions that are required for T cell homeostasis and activation.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. guofu@scripps.edu
authors.forename: Guo
authors.initials: G
authors.lastname: Fu
authors.forename: Jianfang
authors.initials: J
authors.lastname: Hu
authors.forename: Nathalie
authors.initials: N
authors.lastname: Niederberger-Magnenat
authors.forename: Vasily
authors.initials: V
authors.lastname: Rybakin
authors.forename: Javier
authors.initials: J
authors.lastname: Casas
authors.forename: Pia P
authors.initials: PP
authors.lastname: Yachi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Feldstein
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: John A H
authors.initials: JA
authors.lastname: Hoerter
authors.forename: Jeanette
authors.initials: J
authors.lastname: Ampudia
authors.forename: Stephanie
authors.initials: S
authors.lastname: Rigaud
authors.forename: Florence
authors.initials: F
authors.lastname: Lambolez
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Gavin
authors.forename: Karsten
authors.initials: K
authors.lastname: Sauer
authors.forename: Hilde
authors.initials: H
authors.lastname: Cheroutre
authors.forename: Nicholas R J
authors.initials: NR
authors.lastname: Gascoigne
mesh_terms: D000818:Animals; D001483:Base Sequence; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D020013:Calcium Signaling; D049109:Cell Proliferation; D006706:Homeostasis; D007156:Immunologic Memory / Q000502:physiology; D054992:Immunological Synapses / Q000201:enzymology; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000074121:Protein Kinase C-theta; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*
chemical_list: D007527:Isoenzymes; D016328:NF-kappa B; D012333:RNA, Messenger; C081975:protein kinase C eta; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta