title: CD2-mediated regulation of peripheral CD4(+)  CD25(+) regulatory T-cell apoptosis accompanied by down-regulation of Bim.
abstract: Extensive studies on CD4(+)  CD25(+) regulatory T (Treg) cells suggest that they are important in regulating immune responses. However, mechanisms of peripheral Treg cell homeostasis are unknown. We found that stromal cells isolated from secondary lymphoid organs such as spleen and lymph nodes could support the survival of Treg cells. This was dependent on CD2 engagement and a direct interaction between Treg cells and stromal cells. In the presence of stromal cells, Bim, a pro-apoptotic factor, was partially decreased in Treg cells. This effect could be inhibited by anti-CD2 blocking antibodies, indicating that stimulation through CD2 on Treg cells regulates Bim expression, which may be relevant to Treg cell apoptosis. Therefore, Treg cell interactions with stromal cells through CD2 may be essential for Treg cell survival. Surprisingly, the expression of CD2 ligands on stromal cells was not detected. Hence, it is not clear how CD2 on Treg cells contributes to a direct interaction with the stromal cells and participates in survival support for Treg cells. Taken together, CD2 stimuli were mandatory for Treg cell survival with reduced Bim expression, but CD2 may not function as a direct receptor for molecules on stromal cells.
authors.affiliation: Department of Immunology, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kashiwakura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakurai
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kanno
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hashiguchi
authors.forename: Ayano
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Kurosu
authors.forename: Shogo
authors.initials: S
authors.lastname: Tokudome
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Kobata
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kojima
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000072224:Bcl-2-Like Protein 11; D018801:CD2 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016466:CHO Cells; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D018801:CD2 Antigens; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins