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The Journal of Immunology, Vol 153, Issue 12 5402-5412, Copyright © 1994 by American Association of Immunologists
ARTICLES |
DE Epperson and JS Pober
Molecular Cardiobiology Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536.
We characterized the response of resting human CD8 T cells to allogeneic endothelial cells (EC). Both resting and IFN-gamma- pretreated EC stimulate similar CD8 T cell proliferative responses (peak, day 5 to 6), whereas only IFN-gamma-pretreated EC stimulate CD4 T cells. The response increases with increasing numbers of CD8 T cells from 25,000 to 400,000/well. The proliferation of CD8 T cells is inhibited by mAbs reactive with CD8 or HLA-A and -B molecules but not with CD4 or HLA-DR. mAb blocking studies show a role for CD2, LFA-3, and CD59, but not for intercellular adhesion molecule-1, intercellular adhesion molecule-2, very late activation Ag-4, vascular cell adhesion molecule-1, CD28, or CD28 ligand, as costimulatory molecules. The stimulation of resting CD8 T cells by EC causes secretion of IL-2 and IFN-gamma but not IL-4. Both proliferation and IFN-gamma secretion are inhibited by mAb to the IL-2R alpha subunit (CD25). Limiting dilution analysis suggests that approximately 1 in 20,000 resting CD8 T cells secrete IL-2 in response to allogeneic EC. EC stimulate greater than 1 in 10,000 CD8/CD45RO+ cells but fewer than 1 in 40,000 CD8/CD45RA+ cells, which indicates that primarily memory CD8 T cells respond to EC. Coculturing CD8 cells with EC stimulates a sufficient level of endothelial class II MHC expression to subsequently support a CD4 T cell proliferative response. The ability of memory CD8 T cells to proliferate against allogeneic EC, a nonclassical APC, and their ability to stimulate EC may contribute to the initiation of vascularized organ graft rejection.
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D. M. Miller, Y. Zhang, B. M. Rahill, W. J. Waldman, and D. D. Sedmak Human Cytomegalovirus Inhibits IFN-{alpha}-Stimulated Antiviral and Immunoregulatory Responses by Blocking Multiple Levels of IFN-{alpha} Signal Transduction J. Immunol., May 15, 1999; 162(10): 6107 - 6113. [Abstract] [Full Text] [PDF]
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B. C. Biedermann and J. S. Pober Human Endothelial Cells Induce and Regulate Cytolytic T Cell Differentiation J. Immunol., November 1, 1998; 161(9): 4679 - 4687. [Abstract] [Full Text] [PDF]
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W. Ma and J. S. Pober Human Endothelial Cells Effectively Costimulate Cytokine Production by, But Not Differentiation of, Naive CD4+ T Cells J. Immunol., September 1, 1998; 161(5): 2158 - 2167. [Abstract] [Full Text] [PDF]
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A. G. Murray, J. S. Schechner, D. E. Epperson, P. Sultan, J. M. McNiff, C. C. W. Hughes, M. I. Lorber, P. W. Askenase, and J. S. Pober Dermal Microvascular Injury in the Human Peripheral Blood Lymphocyte Reconstituted-Severe Combined Immunodeficient (HuPBL-SCID) Mouse/Skin Allograft Model Is T Cell Mediated and Inhibited by a Combination of Cyclosporine and Rapamycin Am. J. Pathol., August 1, 1998; 153(2): 627 - 638. [Abstract] [Full Text] [PDF]
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M. C. Sirianni, L. Vincenzi, V. Fiorelli, S. Topino, E. Scala, S. Uccini, A. Angeloni, A. Faggioni, D. Cerimele, F. Cottoni, et al. gamma -Interferon Production in Peripheral Blood Mononuclear Cells and Tumor Infiltrating Lymphocytes From Kaposi's Sarcoma Patients: Correlation With the Presence of Human Herpesvirus-8 in Peripheral Blood Mononuclear Cells and Lesional Macrophages Blood, February 1, 1998; 91(3): 968 - 976. [Abstract] [Full Text] [PDF]
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