Effector CD8+ T cells activated in vitro confer immediate and long-term tumor protection in vivo

Eur J Immunol. 2008 Oct;38(10):2886-95. doi: 10.1002/eji.200838483.


We studied the ability of CD8+ T cells activated in vitro to mediate tumor protection after transfer into adoptive hosts. TCR transgenic CD8+ T cells were activated in culture with DC and specific peptide antigen, and briefly expanded in IL-2 containing medium. Cultured cells acquired a CD44hiCD62Llo phenotype, and following in vivo transfer they preferentially homed to non-lymphoid tissues and spleen. In vivo, their numbers declined between day 0 and day 20, and then remained relatively stable from day 20 to day 90. Over time, many of the injected cells re-expressed CD62L, and acquired the ability to localize to secondary lymphoid organs. Transferred T cells underwent low-level proliferation, expressed IL-7Ralpha and IL-15Rbeta, were cytotoxic in vivo, and retained the ability to produce IL-2, IFN-gamma and TNF-alpha upon ex vivo restimulation. In addition, transferred T cells conferred a high degree of tumor protection, which was greatest immediately after injection, and remained significant even when tumor was given 90 days after T-cell transfer. We conclude that in vitro generated effector T cells can mediate immediate and long-term tumor protection, and develop into long-lived memory T-cell populations in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Immunologic Memory
  • Immunotherapy, Adoptive*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Interleukin-2 Receptor beta Subunit / immunology
  • Interleukin-2 Receptor beta Subunit / metabolism*
  • Lymphocyte Activation*
  • Mice
  • Mice, Mutant Strains
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / therapy
  • Receptors, Interleukin-7 / immunology
  • Receptors, Interleukin-7 / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology


  • Il2rb protein, mouse
  • Interleukin-2
  • Interleukin-2 Receptor beta Subunit
  • Receptors, Interleukin-7
  • Tumor Necrosis Factor-alpha
  • interleukin-7 receptor, alpha chain
  • Interferon-gamma