CD59 and CD48 expressed by rat retinal pigment epithelial cells are major ligands for the CD2-mediated alternative pathway of T cell activation

J Liversidge, Rosie Dawson, Sharon Andrea Hoey, Dorothy McKay, P Grabowski, J V Forrester

Research output: Contribution to journalArticle

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Abstract

The alternative CD2-mediated pathway of T cell activation, which is independent of MHC/peptide recognition by the TCR/CD3 complex, is dependent upon two signals being received by the CD2 molecule. The natural ligand for CD2 is CD58, but controversy exists over alternative or additional ligands that could deliver the second signal in vivo. We have used rat retinal pigment epithelial cells (RPE), which lack temperature-insensitive ligands for CD2 adhesion, to study Ag-independent T cell activation. Rat RPE cells expressed high levels of CD59 and low levels of another potential CD2 ligand, CD48, both in vitro and in the in vivo model of experimental autoimmune uveoretinitis. When increasing numbers of syngeneic T cells were added to microwell cultures of rat RPE cells, the T cells, even in the absence of any exogenous stimulant in the cultures, underwent spontaneous proliferation. This effect required metabolically active RPE cells, and was IL-2 driven and enhanced in the presence of indomethacin. Proliferation was modulated by phosphatidylinositol-phospholipase C treatment of the RPE, and blocked by mAbs to CD59. Ab cross-linking of CD48 but not CD59 on the RPE was found to induce messenger RNA expression for IL-1 beta, which together with constitutively expressed IL-6 are required costimulatory factors for T cell activation through CD2. This is the first demonstration in a fully syngeneic system that bi-directional signaling involving CD59 and CD48 molecules expressed by physiologically normal, nonhematopoietic, cells can trigger T lymphocyte activation and proliferation through autocrine IL-2 production in the absence of Ag.
Original languageEnglish
Pages (from-to)3696-3703
Number of pages8
JournalThe Journal of Immunology
Volume156
Issue number10
Publication statusPublished - 1996

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Retinal Pigments
Epithelial Cells
Ligands
T-Lymphocytes
Interleukin-2
T-Cell Antigen Receptor-CD3 Complex
TCF Transcription Factors
Type C Phospholipases
Lymphocyte Activation
Phosphatidylinositols
Interleukin-1beta
Indomethacin
Interleukin-6
Theoretical Models
Messenger RNA
Peptides
Temperature

Keywords

  • Animals
  • Antigens, CD
  • Antigens, CD2
  • Antigens, CD59
  • Base Sequence
  • Cell Line
  • Coculture Techniques
  • Interleukin-2
  • Ligands
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Phosphatidylinositol Diacylglycerol-Lyase
  • Phosphoric Diester Hydrolases
  • Pigment Epithelium of Eye
  • Rats
  • Rats, Inbred Lew
  • T-Lymphocytes

Cite this

Liversidge, J., Dawson, R., Hoey, S. A., McKay, D., Grabowski, P., & Forrester, J. V. (1996). CD59 and CD48 expressed by rat retinal pigment epithelial cells are major ligands for the CD2-mediated alternative pathway of T cell activation. The Journal of Immunology, 156(10), 3696-3703.

CD59 and CD48 expressed by rat retinal pigment epithelial cells are major ligands for the CD2-mediated alternative pathway of T cell activation. / Liversidge, J; Dawson, Rosie; Hoey, Sharon Andrea; McKay, Dorothy; Grabowski, P; Forrester, J V.

In: The Journal of Immunology, Vol. 156, No. 10, 1996, p. 3696-3703.

Research output: Contribution to journalArticle

Liversidge, J, Dawson, R, Hoey, SA, McKay, D, Grabowski, P & Forrester, JV 1996, 'CD59 and CD48 expressed by rat retinal pigment epithelial cells are major ligands for the CD2-mediated alternative pathway of T cell activation', The Journal of Immunology, vol. 156, no. 10, pp. 3696-3703.
Liversidge, J ; Dawson, Rosie ; Hoey, Sharon Andrea ; McKay, Dorothy ; Grabowski, P ; Forrester, J V. / CD59 and CD48 expressed by rat retinal pigment epithelial cells are major ligands for the CD2-mediated alternative pathway of T cell activation. In: The Journal of Immunology. 1996 ; Vol. 156, No. 10. pp. 3696-3703.
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AU - Liversidge, J

AU - Dawson, Rosie

AU - Hoey, Sharon Andrea

AU - McKay, Dorothy

AU - Grabowski, P

AU - Forrester, J V

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AB - The alternative CD2-mediated pathway of T cell activation, which is independent of MHC/peptide recognition by the TCR/CD3 complex, is dependent upon two signals being received by the CD2 molecule. The natural ligand for CD2 is CD58, but controversy exists over alternative or additional ligands that could deliver the second signal in vivo. We have used rat retinal pigment epithelial cells (RPE), which lack temperature-insensitive ligands for CD2 adhesion, to study Ag-independent T cell activation. Rat RPE cells expressed high levels of CD59 and low levels of another potential CD2 ligand, CD48, both in vitro and in the in vivo model of experimental autoimmune uveoretinitis. When increasing numbers of syngeneic T cells were added to microwell cultures of rat RPE cells, the T cells, even in the absence of any exogenous stimulant in the cultures, underwent spontaneous proliferation. This effect required metabolically active RPE cells, and was IL-2 driven and enhanced in the presence of indomethacin. Proliferation was modulated by phosphatidylinositol-phospholipase C treatment of the RPE, and blocked by mAbs to CD59. Ab cross-linking of CD48 but not CD59 on the RPE was found to induce messenger RNA expression for IL-1 beta, which together with constitutively expressed IL-6 are required costimulatory factors for T cell activation through CD2. This is the first demonstration in a fully syngeneic system that bi-directional signaling involving CD59 and CD48 molecules expressed by physiologically normal, nonhematopoietic, cells can trigger T lymphocyte activation and proliferation through autocrine IL-2 production in the absence of Ag.

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KW - Ligands

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