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 CD44highCD62L 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 CD44highCD62Llow 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 highCD62Lhigh 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.
| Original language | English |
|---|---|
| Pages (from-to) | 739-748 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 175 |
| Issue number | 2 |
| Publication status | Published - Jul 15 2005 |
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ASJC Scopus subject areas
- Immunology
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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; Mondino, Anna.
In: Journal of Immunology, Vol. 175, No. 2, 15.07.2005, p. 739-748.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phenotype and homing of CD4 tumor-specific T cells is modulated by tumor bulk
AU - Benigni, Fabio
AU - Zimmermann, Valérie S.
AU - Hugues, Stephanie
AU - Caserta, Stefano
AU - Basso, Veronica
AU - Rivino, Laura
AU - Ingulli, Elizabeth
AU - Malherbe, Laurent
AU - Glaichenhaus, Nicolas
AU - Mondino, Anna
PY - 2005/7/15
Y1 - 2005/7/15
N2 - 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 CD44highCD62L 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 CD44highCD62Llow 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 highCD62Lhigh 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.
AB - 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 CD44highCD62L 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 CD44highCD62Llow 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 highCD62Lhigh 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=23244447692&partnerID=8YFLogxK
M3 - Article
C2 - 16002669
AN - SCOPUS:23244447692
VL - 175
SP - 739
EP - 748
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -