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*
Department of Immunology, University of Toronto, Toronto, Ontario, Canada; and
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
A costimulatory member of the TNFR family, 4-1BB, is expressed on
activated T cells. Although some reports have suggested that 4-1BB is
primarily involved in CD8 T cell activation, in this report we
demonstrate that both CD4 and CD8 T cells respond to 4-1BB ligand
(4-1BBL) with similar efficacy. CD4 and CD8 TCR transgenic T cells
up-regulate 4-1BB, OX40, and CD27 and respond to 4-1BBL-mediated
costimulation during a primary response to peptide Ag. 4-1BBL enhanced
proliferation, cytokine production, and CTL effector function of TCR
transgenic T cells. To compare CD4 vs CD8 responses to 4-1BBL under
similar conditions of antigenic stimulation, we performed MLRs with
purified CD4 or CD8 responders from CD28+/+ and
CD28-/- mice. We found that CD8 T cells produced IL-2 and
IFN-
in a 4-1BBL-dependent manner, whereas under the same conditions
the CD4 T cells produced IL-2 and IL-4. 4-1BBL promoted survival of CD4
and CD8 T cells, particularly at late stages of the MLR. CD4 and CD8 T
cells both responded to anti-CD3 plus s4-1BBL with a similar
cytokine profile as observed in the MLR. CD4 and CD8 T cells exhibited
enhanced proliferation and earlier cell division when stimulated with
anti-CD3 plus anti-CD28 compared with anti-CD3 plus 4-1BBL,
and both subsets responded comparably to anti-CD3 plus 4-1BBL.
These data support the idea that CD28 plays a primary role in initial T
cell expansion, whereas 4-1BB/4-1BBL sustains both CD4 and CD8 T cell
responses, as well as enhances cell division and T cell effector
function.
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G. Demirci, F. Amanullah, R. Kewalaramani, H. Yagita, T. B. Strom, M. H. Sayegh, and X. C. Li Critical Role of OX40 in CD28 and CD154-Independent Rejection J. Immunol., February 1, 2004; 172(3): 1691 - 1698. [Abstract] [Full Text] [PDF]
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E. M. Bertram, W. Dawicki, B. Sedgmen, J. L. Bramson, D. H. Lynch, and T. H. Watts A Switch in Costimulation from CD28 to 4-1BB during Primary versus Secondary CD8 T Cell Response to Influenza In Vivo J. Immunol., January 15, 2004; 172(2): 981 - 988. [Abstract] [Full Text] [PDF]
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R. A. Wilcox, K. Tamada, D. B. Flies, G. Zhu, A. I. Chapoval, B. R. Blazar, W. M. Kast, and L. Chen Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo Blood, January 1, 2004; 103(1): 177 - 184. [Abstract] [Full Text] [PDF]
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C. Wiethe, K. Dittmar, T. Doan, W. Lindenmaier, and R. Tindle Enhanced Effector and Memory CTL Responses Generated by Incorporation of Receptor Activator of NF-{kappa}B (RANK)/RANK Ligand Costimulatory Molecules into Dendritic Cell Immunogens Expressing a Human Tumor-Specific Antigen J. Immunol., October 15, 2003; 171(8): 4121 - 4130. [Abstract] [Full Text] [PDF]
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L. Myers, C. Takahashi, R. S. Mittler, R. J. Rossi, and A. T. Vella Effector CD8 T cells possess suppressor function after 4-1BB and Toll-like receptor triggering PNAS, April 29, 2003; 100(9): 5348 - 5353. [Abstract] [Full Text] [PDF]
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C. Wiethe, K. Dittmar, T. Doan, W. Lindenmaier, and R. Tindle Provision of 4-1BB Ligand Enhances Effector and Memory CTL Responses Generated by Immunization with Dendritic Cells Expressing a Human Tumor-Associated Antigen J. Immunol., March 15, 2003; 170(6): 2912 - 2922. [Abstract] [Full Text] [PDF]
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D. J. Shedlock, J. K. Whitmire, J. Tan, A. S. MacDonald, R. Ahmed, and H. Shen Role of CD4 T Cell Help and Costimulation in CD8 T Cell Responses During Listeria monocytogenes Infection J. Immunol., February 15, 2003; 170(4): 2053 - 2063. [Abstract] [Full Text] [PDF]
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P. Bansal-Pakala and M. Croft Defective T Cell Priming Associated with Aging Can Be Rescued by Signaling Through 4-1BB (CD137) J. Immunol., November 1, 2002; 169(9): 5005 - 5009. [Abstract] [Full Text] [PDF]
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D. Laderach, M. Movassagh, A. Johnson, R. S. Mittler, and A. Galy 4-1BB co-stimulation enhances human CD8+ T cell priming by augmenting the proliferation and survival of effector CD8+ T cells Int. Immunol., October 1, 2002; 14(10): 1155 - 1167. [Abstract] [Full Text] [PDF]
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T. Wen, J. Bukczynski, and T. H. Watts 4-1BB Ligand-Mediated Costimulation of Human T Cells Induces CD4 and CD8 T Cell Expansion, Cytokine Production, and the Development of Cytolytic Effector Function J. Immunol., May 15, 2002; 168(10): 4897 - 4906. [Abstract] [Full Text] [PDF]
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R. A. Wilcox, A. I. Chapoval, K. S. Gorski, M. Otsuji, T. Shin, D. B. Flies, K |
