Skip to main content
Article thumbnail
Location of Repository

Tumor Rejection Induced by CD70-mediated Quantitative and Qualitative Effects on Effector CD8+ T Cell Formation

By Ramon Arens, Koen Schepers, Martijn A. Nolte, Michiel F. van Oosterwijk, René A.W. van Lier, Ton N.M. Schumacher and Marinus H.J. van Oers


In vivo priming of antigen-specific CD8+ T cells results in their expansion and differentiation into effector T cells followed by contraction into a memory T cell population that can be maintained for life. Recent evidence suggests that after initial antigenic stimulation, the magnitude and kinetics of the CD8+ T cell response are programmed. However, it is unclear to what extent CD8+ T cell instruction in vivo is modulated by costimulatory signals. Here, we demonstrate that constitutive ligation of the tumor necrosis factor receptor family member CD27 by its ligand CD70 quantitatively augments CD8+ T cell responses to influenza virus infection and EL-4 tumor challenge in vivo by incrementing initial expansion and maintaining higher numbers of antigen-specific T cells in the memory phase. Concomitantly, the quality of antigen-specific T cells improved as evidenced by increased interferon (IFN)-γ production and a greater cytotoxic potential on a per cell basis. As an apparent consequence, the superior effector T cell formation induced by CD70 protected against a lethal dose of poorly immunogenic EL4 tumor cells in a CD8+ T cell– and IFN-γ–dependent manner. Thus, CD70 costimulation enhances both the expansion and per cell activity of antigen-specific CD8+ T cells

Topics: Article
Publisher: The Rockefeller University Press
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    1. (2001). 1605 and is essential for long-term survival of CD4 T cells.
    2. (2002). 4-1BB promotes the survival of CD8 T lymphocytes by increasing expression of Bcl-xL and
    3. Anti-tumor immunity elicited by a recombinant vaccinia virus expressing CD70 (CD27L).
    4. (2000). CD27 is required for generation and long-term maintenance of T cell immunity.
    5. (1995). CD27-CD27 ligand/CD70 interactions enhance alloantigeninduced proliferation and cytolytic activity in CD8 T lymphocytes.
    6. (2003). CD4 T cells are required for secondary expansion and memory in CD8 T lymphocytes.
    7. (1994). CD4 T cells are required to sustain CD8 cytotoxic T-cell responses during chronic viral infection.
    8. (1998). CD40 and CD70 co-stimulate a potent in vivo antitumor T cell response.
    9. (2003). CD8 T cell responses to infectious pathogens.
    10. (1998). Characterization of murine CD70 by molecular cloning and mAb.
    11. (1994). Characterization of the human CD27 ligand, a novel member of the TNF gene family.
    12. (2003). Co-stimulatory members of the TNFR family: keys to effective T-cell immunity?
    13. (2001). Constitutive CD27/CD70 interaction induces expansion of effector-type T cells and results in IFNgamma-mediated B cell depletion.
    14. (2000). Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans.
    15. Dynamic programming of CD8( ) T lymphocyte responses.
    16. (2000). Early programming of T cell populations responding to bacterial infection.
    17. (2002). Effector and memory T-cell differentiation: implications for vaccine development.
    18. (1995). Engagement of CD27 with its ligand CD70 provides a second signal for T cell activation.
    19. (1998). Enhancement of antitumor immunity by expression of CD70 (CD27 ligand) or CD154 (CD40 ligand) costimulatory molecules in tumor cells. Cancer Gene Ther.
    20. (2000). Expression of CD27 on murine hematopoietic stem and progenitor cells.
    21. (1999). Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses.
    22. (1996). Immunological memory and protective immunity: understanding their relation.
    23. (2002). Involvement of CD27/CD70 interactions in antigen-specific cytotoxic T-lymphocyte (CTL) activity by perforin-mediated cytotoxicity.
    24. (2003). Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions.
    25. (2001). Memory CD8 T cell differentiation: initial antigen encounter triggers a developmental program in naive cells.
    26. (1999). Migration kinetics and final destination of type 1 and type 2 CD8 effector cells predict protection against pulmonary virus infection.
    27. (1993). Molecular and biological characterization of a ligand for CD27 defines a new family of cytokines with homology to tumor necrosis factor.
    28. (1993). Multiple defects of immune cell function in mice with disrupted interferon-gamma genes.
    29. Naive CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation.
    30. (1991). Normal development and function of CD8 cells but markedly decreased helper cell activity in mice lacking CD4.
    31. Novel mAbs reveal potent co-stimulatory activity of murine CD27.
    32. (1992). Participation of the CD27 antigen in the regulation of IL-2-activated human natural killer cells.
    33. (1996). Phenotypic analysis of antigen-specific T lymphocytes.
    34. (2001). Redundancy of direct priming and crosspriming in tumor-specific CD8 T cell responses.
    35. (2000). Regulation of antigen-specific CD8 T cell homeostasis by perforin and interferon-gamma.
    36. (2002). responses in the regression of retrovirusinduced sarcomas.
    37. (2001). Simultaneous detection of influenza viruses A and B using real-time quantitative PCR.
    38. (1999). Systemic T cell expansion during localized viral infection.
    39. (2004). The size and phenotype of virus-specific T cell populations is determined by repetitive antigenic stimulation and environmental cytokines.
    40. (2003). Therapeutic use of IL-2 to enhance antiviral T-cell responses in vivo.
    41. (1992). Thymic depletion and peripheral activation of class I major histocompatibility complex-restricted T cells by soluble peptide in T-cell receptor transgenic mice.
    42. (1987). Tissue distribution and biochemical and functional properties of Tp55 (CD27), a novel T cell differentiation antigen.
    43. (2002). Visualization and quantification of T cell-mediated cytotoxicity using cell-permeable fluorogenic caspase substrates.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.