title: Ligation of CD28 by its natural ligand CD86 in the absence of TCR stimulation induces lipid raft polarization in human CD4 T cells.
abstract: Stimulation of resting CD4 T cells with anti-CD3/CD28-coated beads leads to rapid polarization of lipid rafts (LRs). It has been postulated that a major role of costimulation is to facilitate LR aggregation. CD86 is up-regulated or expressed aberrantly on immune cells in a wide array of autoimmune and infectious diseases. Using an Ig fusion with the extracellular domain of CD86 (CD86Ig) bound to a magnetic bead or K562 cells expressing CD86, we demonstrated that ligation of CD28 by its natural ligand, but not by Ab, induced polarization of LRs at the cell-bead interface of fresh human CD4 T cells in the absence of TCR ligation. This correlated with activation of Vav-1, increase of the intracellular calcium concentration, and nuclear translocation of NF-kappaB p65, but did not result in T cell proliferation or cytokine production. These studies show, for the first time, that LR polarization can occur in the absence of TCR triggering, driven solely by the CD28/CD86 interaction. This result has implications for mechanisms of T cell activation. Abnormalities in this process may alter T and B cell tolerance and susceptibility to infection.
authors.affiliation: Division of Rheumatology, Children's Hospital of Philadelphia, and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Birgit
authors.initials: B
authors.lastname: Kovacs
authors.forename: Richard V
authors.initials: RV
authors.lastname: Parry
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Ma
authors.forename: Emily
authors.initials: E
authors.lastname: Fan
authors.forename: Debra K
authors.initials: DK
authors.lastname: Shivers
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Freiberg
authors.forename: Anna K
authors.initials: AK
authors.lastname: Thomas
authors.forename: Robert
authors.initials: R
authors.lastname: Rutherford
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Rumbley
authors.forename: James L
authors.initials: JL
authors.lastname: Riley
authors.forename: Terri H
authors.initials: TH
authors.lastname: Finkel
mesh_terms: D051940:B7-2 Antigen / Q000378:metabolism / Q000502:physiology*; D018106:CD28 Antigens / Q000378:metabolism / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D018106:CD28 Antigens; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; D051996:Transcription Factor RelA; C496618:VAV1 protein, human; D002118:Calcium