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 language | English |
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Pages (from-to) | 739-48 |
Number of pages | 10 |
Journal | Journal of Immunology |
Volume | 175 |
Issue number | 2 |
DOIs | |
Publication status | Published - 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