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

Fabio Benigni, Valérie S Zimmermann, Stephanie Hugues, Stefano Caserta, Veronica Basso, Laura Rivino, Elizabeth Ingulli, Laurent Malherbe, Nicolas Glaichenhaus, Anna Mondino

Research output: Contribution to journalArticle (Academic Journal)peer-review

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.

Original languageEnglish
Pages (from-to)739-48
Number of pages10
JournalJournal of Immunology
Volume175
Issue number2
DOIs
Publication statusPublished - 15 Jul 2005

Keywords

  • Adenocarcinoma/genetics
  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan/biosynthesis
  • Breast Neoplasms/genetics
  • CD4-Positive T-Lymphocytes/immunology
  • Cell Differentiation/immunology
  • Cell Line, Tumor
  • Cell Movement/genetics
  • Dendritic Cells/immunology
  • Epitopes, T-Lymphocyte/biosynthesis
  • Histocompatibility Antigens Class II/biosynthesis
  • Immunologic Memory/genetics
  • Immunophenotyping
  • Interferon-gamma/metabolism
  • Lymph Nodes/immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Molecular Sequence Data
  • Neoplasm Transplantation
  • Organ Specificity/genetics
  • Protozoan Proteins/biosynthesis

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