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Updated: Aug 22, 2026
In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
Published on: January 22, 2020
Constitutive expression of CCR7 directs effector CD8 T cells into the splenic white pulp and impairs functional
Heike Unsoeld1, David Voehringer, Stefan Krautwald
1Institute for Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Freiburg, Germany.
Abstract:
Antigenic stimulation down-regulates CCR7 on effector T cells. To analyze the importance of CCR7 down-regulation, transgenic (tg) mice constitutively expressing CCR7 were generated. CD8 T cells with defined Ag specificity were obtained by breeding CCR7-tg mice with P14 TCR-tg mice specific for lymphocytic choriomeningitis virus. Transgenic CCR7 expression did not impair proliferation of P14.CCR7 T cells induced by lymphocytic choriomeningitis virus infection, but prevented CCR7 down-regulation. Compared with wild-type P14 effector cells, P14.CCR7 effector cells, expressing the CCR7 transgene, were increased in the spleen, but decreased in blood and peripheral tissues. Moreover, P14.CCR7 effector cells localized almost exclusively in the splenic white pulp, whereas P14 effector cells were excluded from splenic white pulp cords and were found preferentially in the red pulp. Functional experiments further revealed that P14.CCR7 effector cells were impaired in rapid viral clearance and in inducing Ag-specific delayed-type hypersensitivity reactions. Thus, the present study demonstrates that down-regulation of CCR7 during CD8 T cell activation is important to release effector cells from the white pulp of the spleen, and highlights the importance of effector cell localization in providing rapid immunity.
Insights
Down-regulation of chemokine receptor CCR7 on effector T cells is crucial for their migration out of the spleen. This release is vital for effective viral clearance and immune response.
Area of Science:
- Immunology
- Cellular Biology
- T cell Activation and Migration
Background:
- Antigenic stimulation typically leads to the down-regulation of CCR7 on effector T cells.
- The functional significance of this CCR7 down-regulation in T cell effector function and localization remains incompletely understood.
Purpose of the Study:
- To investigate the importance of CCR7 down-regulation in CD8 T cell effector function.
- To analyze the role of CCR7 expression levels in T cell trafficking and immune response efficacy.
Main Methods:
- Generation of transgenic (tg) mice constitutively expressing CCR7.
- Breeding CCR7-tg mice with P14 TCR-tg mice for Ag-specific CD8 T cells (P14.CCR7).
- Analysis of T cell proliferation, localization (spleen, blood, peripheral tissues), and functional assays (viral clearance, DTH reactions).
Main Results:
- Constitutive CCR7 expression in P14.CCR7 T cells prevented CCR7 down-regulation upon activation.
- P14.CCR7 effector cells showed increased splenic accumulation and decreased presence in blood and peripheral tissues compared to wild-type.
- P14.CCR7 effector cells were retained in the splenic white pulp, impairing viral clearance and DTH responses.
Conclusions:
- Down-regulation of CCR7 during CD8 T cell activation is essential for releasing effector cells from the spleen's white pulp.
- Proper effector T cell localization, facilitated by CCR7 modulation, is critical for mounting rapid and effective immunity against viral infections.
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