title: Enrichment of regulatory CD4(+)CD25(+) T cells by inhibition of phospholipase D signaling.
abstract: Antigen stimulation of lymphocytes induces upregulation of phospholipase D (PLD) activity, but the biological significance of PLD-mediated signaling in T cells has not been well established. Here we demonstrate that PLD signaling is essential for proliferation of mouse CD8(+) T cells and CD4(+)CD25(-) T cells, but is not required for proliferation of CD4(+)CD25(+) regulatory T cells. We exploited this observation to develop an efficient method to enrich for regulatory T cells starting from preparations of total CD4(+) T lymphocytes. Inhibition of PLD signaling blocked effector T-cell proliferation after T cell-antigen receptor (TCR) engagement, but had no significant effect on the proliferation of CD4(+)CD25(+) T cells with regulatory functions. Consequently, cells expanded in vitro for one week by antigen receptor stimulation with PLD signal inhibition were markedly enriched for regulatory T cells.
authors.affiliation: Immunotherapy Center, Institute of Molecular Medicine and Genetics, Department of Medicine, Medical College of Georgia, 1120 15th Street, Augusta, Georgia 30912, USA.
authors.forename: Nagendra
authors.initials: N
authors.lastname: Singh
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Seki
authors.forename: Mariko
authors.initials: M
authors.lastname: Takami
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
authors.forename: Phil R
authors.initials: PR
authors.lastname: Chandler
authors.forename: Davood
authors.initials: D
authors.lastname: Khosravi
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zheng
authors.forename: Mayuko
authors.initials: M
authors.lastname: Takezaki
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Lee
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mellor
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bollag
authors.forename: Makio
authors.initials: M
authors.lastname: Iwashima
mesh_terms: D015704:CD4 Antigens / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D002469:Cell Separation / Q000379:methods*; D010739:Phospholipase D / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D015375:Receptors, Interleukin-2; D010739:Phospholipase D