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Dynamic changes during the immune response in T cell-antigen-presenting cell clusters isolated from lymph nodes
1Tumor Immunology Program, Division of Cellular Immunology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
The Journal of Experimental Medicine
|February 5, 2003
Summary
Mature dendritic cells and T cells form clusters crucial for adaptive immunity. These T cell clusters initiate activation and proliferation in vivo, with timing invariant to factors like antigen dose.
Area of Science:
- Immunology
- Cell Biology
- Adaptive Immunity
Background:
- Antigen-specific T cell activation by dendritic cells is central to adaptive immunity.
- Multicellular clusters of T cells and antigen-presenting cells are observed in lymphoid organs.
Purpose of the Study:
- To isolate and characterize preformed multicellular clusters of T cells and antigen-presenting cells.
- To investigate the in vivo dynamics of T cell activation and proliferation within these clusters.
Main Methods:
- Ex vivo isolation of T cell-dendritic cell clusters.
- Adoptive transfer of antigen-specific T cells into clusters.
- In vivo tracking of T cell activation, proliferation, and transit time within clusters.
Main Results:
- Adoptively transferred T cells segregated into clusters, initiating activation and proliferation in vivo.
- T cell transit through the cluster compartment took 32-36 hours.
- Response timing to agonistic epitopes was invariant across T cell lineage, MHC haplotype, and antigen dose.
- T cell division initiation was delayed by 6 hours for subdominant epitopes and weak agonists.
Conclusions:
- Preformed multicellular clusters facilitate T cell activation and proliferation in a confined microenvironment.
- The timing of T cell responses within clusters is highly regulated and largely invariant.
- These findings provide a model for studying short-range cell-cell interactions in immune responses.