Phenotype and homing of CD4 tumor-specific T cells is modulated by tumor bulk

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 Medicine
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: 24 Sep 2015 12:32
URI: http://sro.sussex.ac.uk/id/eprint/56881
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