TNFR2-deficient memory CD8 T cells provide superior protection against tumor cell growth.

Abstract

TNF receptor-2 (TNFR2) plays a critical role in promoting the activation and survival of naive T cells during the primary response. Interestingly, anti-CD3 plus IL-2 activated TNFR2(-/-) CD8 T cells are highly resistant to activation-induced cell death (AICD), which correlates with high expression levels of prosurvival molecules such as Bcl-2, survivin, and CD127 (IL-7Ralpha). We determined whether the resistance of activated TNFR2(-/-) CD8 T cells to AICD contributes to more effective protection against tumor cell growth. We found that during a primary tumor challenge, despite initial inferiority in controlling tumor cell growth, TNFR2(-/-) mice were able to more effectively control tumor burden over time compared with wild-type (WT) mice. Furthermore, vaccination of TNFR2(-/-) mice with recombinant Listeria monocytogenes that express OVA confers better protection against the growth of OVA-expressing E.G7 tumor cells relative to similarly vaccinated WT mice. The enhanced protection against tumor cell growth was not due to more effective activation of OVA-specific memory CD8 T cells in vaccinated TNFR2(-/-) mice. In vitro studies indicate that optimally activated OVA-specific TNFR2(-/-) CD8 T cells proliferated to the same extent and possess similar cytotoxicity against E.G7 tumor cells as WT CD8 T cells. However, relative to WT cells, activated OVA-specific TNFR2(-/-) CD8 T cells were highly resistant to AICD. Thus, the enhanced protection against E.G7 in TNFR2(-/-) mice is likely due to the recruitment and activation of OVA-specific memory TNFR2(-/-) CD8 T cells and their prolonged survival at the tumor site.

• Authors: Edward Y Kim, Soo-Jeet Teh, Jocelyn Yang, Michael T Chow, Hung-Sia Teh
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 183 Issue 10 Pg. 6051-7 (Nov 15 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19841176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-2
• OVA-8
• Peptide Fragments
• Receptors, Tumor Necrosis Factor, Type II
• Ovalbumin

Topics

• Animals
• Apoptosis (immunology)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cell Line, Tumor
• Immunologic Memory
• Interleukin-2 (pharmacology)
• Lymphocyte Activation (drug effects, immunology)
• Mice
• Mice, Knockout
• Mice, Mutant Strains
• Mice, Transgenic
• Neoplasms (immunology, metabolism)
• Ovalbumin (immunology)
• Peptide Fragments (immunology)
• Receptors, Tumor Necrosis Factor, Type II (genetics, immunology, metabolism)