title: Bcl6 is essential for the generation of long-term memory CD4+ T cells.
abstract: Bcl6 plays a role in the generation and maintenance of memory CD8(+) T cells. We analyzed here a role for Bcl6 in the generation of long-term memory CD4(+) T cells. Naive CD45RB(+) CD4(+) T cells from Bcl6-deficient DO11.10 (KJ1.26(+)) transgenic mice were transferred into BALB/c mice and immunized with ovalbumin peptide and LPS. Long-term memory KJ1.26(+) CD4(+) T cells from wild-type mice were detected in the spleen, lungs and liver during 10 weeks after immunization; however, Bcl6-deficient KJ1.26(+) CD4(+) T cells were vanished completely in those organs 4 weeks after immunization. Since memory CD4(+) T cells can be generated from effector CD4(+) T cells, properties of Bcl6-deficient effector CD4(+) T cells were compared with those wild-type effector CD4(+) T cells 10 days after immunization. Numbers of IFN-gamma-non-producing CD45RB(-), CD62L(+) or IL-7Ralpha(+) effector CD4(+) T cells in the spleen, lungs and liver were similar between Bcl6-deficient and wild-type CD4(+) T cells. However, the percentage of apoptotic cells in Bcl6-deficient effector CD4(+) T cells was higher than that in wild-type effector CD4(+) T cells. At the late effector phase, the number of IFN-gamma-non-producing cells and the percentage of apoptotic cells in Bcl6-deficient CD4(+) T cells were smaller and higher than those in wild-type CD4(+) T cells, respectively. These data suggest that Bcl6 in CD4(+) T cells plays a role in protection of memory precursor CD4(+) T cells from apoptosis and may involve in survivability of long-term memory CD4(+) T cells.
authors.affiliation: Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Ichii
authors.forename: Akemi
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Arima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002452:Cell Count; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D051560:Proto-Oncogene Proteins c-bcl-6; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; C111390:OVA 323-339; D010446:Peptide Fragments; D051560:Proto-Oncogene Proteins c-bcl-6; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; D019041:L-Selectin; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin