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Published on: September 20, 2019
CCL21-induced immune cell infiltration
Abdelkader E Ashour1, Heth R Turnquist, Rakesh K Singh
1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Insights
Subcutaneous injection of CCL21 chemokine attracts dendritic cells (DCs) and T cells to lymph nodes, promoting lymphoid-like structures. This finding guides the therapeutic timing of CCL21 with vaccines for enhanced immune responses.
Area of Science:
- Immunology
- Cell Biology
- Chemoattractant Signaling
Background:
- Cellular immune responses initiate through antigen presentation by dendritic cells (DCs) to T cells.
- Chemokines, like CCL21, regulate DC and T cell trafficking, crucial for initiating T cell responses in lymphoid organs.
- Understanding CCL21's cellular kinetics is vital for optimizing its therapeutic applications.
Purpose of the Study:
- To investigate the cellular infiltration kinetics in response to subcutaneous CCL21 injection.
- To determine the impact of CCL21 on dendritic cell and T cell populations in draining lymph nodes.
- To inform the optimal timing for using CCL21 in therapeutic strategies, particularly with vaccines.
Main Methods:
- Mice were injected subcutaneously with CCL21.
- DC and T cell infiltration into the local draining lymph node was analyzed.
- Cellular populations and tissue structures at the injection site were examined at a 4-day time point.
Main Results:
- CCL21 injection significantly increased the numbers of lymphoid and myeloid DCs in the local lymph node.
- A significant increase in effector T lymphocytes was observed in the draining lymph node 4 days post-injection.
- Small lymphoid-like structures formed in the subcutaneous injection areas by day 4.
Conclusions:
- Subcutaneous CCL21 administration effectively recruits DCs and T cells to the local lymph node.
- The formation of lymphoid-like structures suggests a localized immune activation environment.
- These findings provide critical data for optimizing the timing of CCL21 administration in vaccine-based immunotherapies.
Abstract:
Cellular immune responses can be initiated via peptide presentation by specialized antigen presenting cells, dendritic cells (DCs), which stimulate naïve T cells. The trafficking of DCs and T cells is regulated by chemokines such as CCL21. CCL21 is normally expressed in the lymphoid organs and coordinates the interactions between DCs and T cells, thereby contributing to the initiation of T cell responses. In order to comprehend the mechanisms of CCL21 activity and to utilize CCL21 optimally in therapy, understanding the kinetics of the responses of various cell types to CCL21 would be beneficial. Therefore, in this study, we injected mice subcutaneously (s.c.) with CCL21 and examined the DC and T cell infiltration of the local draining lymph node. CCL21 injection resulted in significantly increased numbers of lymphoid and myeloid DCs and effector T lymphocytes in the local node at 4 days. Furthermore, at 4 days small lymphoid-like structures were visible in the injection areas. These results provide guidance for the optimal timing of CCL21 use in combination with vaccines.
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