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

Benigni, F.; Zimmermann, V. S.; Hugues, S.; Caserta, S.; Basso, V.; Rivino, L.; Ingulli, E.; Malherbe, L.; Glaichenhaus, N.; Mondino, A.

Authors

F. Benigni

V. S. Zimmermann

S. Hugues

S. Caserta

V. Basso

L. Rivino

E. Ingulli

L. Malherbe

N. Glaichenhaus

A. Mondino



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-γ 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-γ - 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-γ 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. Copyright © 2005 by The American Association of Immunologists, Inc.

Journal Article Type Article
Publication Date Jul 15, 2005
Journal Journal of Immunology
Print ISSN 0022-1767
Electronic ISSN 1550-6606
Publisher American Association of Immunologists
Peer Reviewed Peer Reviewed
Volume 175
Issue 2
Pages 739-748
Institution Citation Benigni, F., Zimmermann, V. S., Hugues, S., Caserta, S., Basso, V., Rivino, L., …Mondino, A. (2005). Phenotype and homing of CD4 tumor-specific T cells is modulated by tumor bulk. Journal of Immunology, 175(2), 739-748. https://doi.org/10.4049/jimmunol.175.2.739
DOI https://doi.org/10.4049/jimmunol.175.2.739
Publisher URL http://www.jimmunol.org/content/175/2/739
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