Control of syngeneic tumor growth by activation of CD8+ T cells: Efficacy is limited by migration away from the site and induction of nonresponsiveness

Protul Shrikant, Matthew F. Mescher

Research output: Contribution to journalArticlepeer-review

123 Scopus citations


Activation of Ag-specific CD8+ T cells in response to syngeneic tumor has been visualized by adoptive transfer of CD8+ T cells from OT-I mice, with a transgenic TCR specific for H-2Kb and an OVA peptide, into Thy-1 congenic recipients. Intraperitoneal challenge with E.G7, the EL-4 thymoma transfected with OVA, results in activation and clonal expansion of the OT-I cells in the peritoneal cavity and transient control of tumor growth. However, within 2 days after becoming activated, the OT-I cells migrate out of the peritoneal cavity into the spleen and lymph nodes, and tumor growth resumes in the peritoneal cavity. The OT-I cells in lymph nodes and spleen have lytic effector activity, but exhibit split anergy in that they cannot proliferate in response to Ag unless exogenous IL-2 is provided. The failure to remain at the tumor site and continue to control tumor growth is not due to selection of Ag loss variants or development of suppression. These results suggest that effective CD8-targeted immunotherapy may depend less on enhancing the initial activation and more on sustaining the response at the appropriate location and/or reactivating cells that have left the site of tumor growth and become nonresponsive.

Original languageEnglish (US)
Pages (from-to)2858-2866
Number of pages9
JournalJournal of Immunology
Issue number5
StatePublished - Mar 1 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Control of syngeneic tumor growth by activation of CD8<sup>+</sup> T cells: Efficacy is limited by migration away from the site and induction of nonresponsiveness'. Together they form a unique fingerprint.

Cite this