Antigen-Experienced CD4(+) T Cells Limit Naive T-Cell Priming in Response to Therapeutic Vaccination In vivo

作者：Schiering Chris; Guarnerio Jlenia; Basso Veronica; Muzio Luca; Mondino Anna^*

来源：Cancer Research, 2010, 70(15): 6161-6170.

DOI：10.1158/0008-5472.CAN-09-4398

CD4(+) T cells play a central role in protective immunity. In a mouse tumor model, we previously found that tumor growth elicits natural CD4(+) T-cell responses, but impedes therapeutic vaccination. We show here that inhibition of vaccine-mediated naive T-cell priming is due to the presence of a minor but distinct population of tumor-reactive CD4(+) T cells. These cells are generated in the tumor draining lymph nodes (LN), are capable of systemic redistribution, and act to limit the representation of antigen-bearing MHC II+ antigen-presenting cells (APC) in contralateral LNs or when transferred to tumor-free mice. Surgical tumor resection, which lowers the representation of tumor primed CD4(+) T cells, restored to some extent vaccine-induced CD4(+) T-cell activation. Likewise, vaccination with artificial APCs (latex beads) or higher numbers of dendritic cells allowed comparable CD4(+) T-cell priming in tumor-free and tumor-bearing mice. Together, our results emphasize the ability of antigen-experienced CD4(+) T lymphocytes to interfere with therapeutic vaccination and highlight the need for alternative strategies able to surmount limitations imposed by ongoing immune responses. Cancer Res; 70(15); 6161-70.

• 出版日期2010-8-1