Benigni, Fabio, Zimmermann, Valérie S, Hugues, Stephanie, Caserta, Stefano, Basso, Veronica, Rivino, Laura, Ingulli, Elizabeth, Malherbe, Laurent, Glaichenhaus, Nicolas and Mondino, Anna (2005) Phenotype and homing of CD4 tumor-specific T cells is modulated by tumor bulk. Journal of immunology (Baltimore, Md. : 1950), 175 (2). pp. 739-48. ISSN 0022-1767

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Abstract

Technical difficulties in tracking endogenous CD4 T lymphocytes have limited the characterization of tumor-specific CD4 T cell responses. Using fluorescent MHC class II/peptide multimers, we defined the fate of endogenous Leishmania receptor for activated C kinase (LACK)-specific CD4 T cells in mice bearing LACK-expressing TS/A tumors. LACK-specific CD44(high)CD62L(low) CD4 T cells accumulated in the draining lymph nodes and had characteristics of effector cells, secreting IL-2 and IFN-gamma upon Ag restimulation. Increased frequencies of CD44(high)CD62L(low) LACK-experienced cells were also detected in the spleen, lung, liver, and tumor itself, but not in nondraining lymph nodes, where the cells maintained a naive phenotype. The absence of systemic redistribution of LACK-specific memory T cells correlated with the presence of tumor. Indeed, LACK-specific CD4 T cells with central memory features (IL-2(+)IFN-gamma(-)CD44(high)CD62L(high) cells) accumulated in all peripheral lymph nodes of mice immunized with LACK-pulsed dendritic cells and after tumor resection. Together, our data demonstrate that although tumor-specific CD4 effector T cells producing IFN-gamma are continuously generated in the presence of tumor, central memory CD4 T cells accumulate only after tumor resection. Thus, the continuous stimulation of tumor-specific CD4 T cells in tumor-bearing mice appears to hinder the systemic accumulation of central memory CD4 T lymphocytes.

Item Type:	Article
Keywords:	tumour immunology T cells
Schools and Departments:	Brighton and Sussex Medical School > Clinical and Experimental Medicine Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects:	Q Science > QR Microbiology > QR0180 Immunology R Medicine > RM Therapeutics. Pharmacology > RM0270 Immunotherapy. Serotherapy
Depositing User:	Stefano Caserta
Date Deposited:	24 Sep 2015 12:32
Last Modified:	21 Sep 2017 13:57
URI:	http://srodev.sussex.ac.uk/id/eprint/56881

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