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Dynamic Changes During the Immune Response in T Cell–Antigen-presenting Cell Clusters Isolated from Lymph Nodes

Mirja Hommel and Bruno Kyewski

Tumor Immunology Program, Division of Cellular Immunology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany

Address correspondence to Bruno Kyewski, Tumor Immunology Program, Division of Cellular Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Phone: 49-62-21-42-37-34; Fax: 49-62-21-42-37-02; E-mail: b.kyewski{at}dkfz-heidelberg

Activation of antigen-specific T cells by mature dendritic cells in secondary lymphoid organs is a key control point of the adaptive immune response. Here we describe the ex vivo isolation of preformed multicellular clusters between T cells and antigen-presenting cells. Adoptively transferred, antigen-specific T cells segregated into individual clusters where their activation and proliferation was initiated in vivo. Transit of the T cell cohort through the cluster compartment required 32–36 h. The precise timing of the response to agonistic epitopes was remarkably invariant regardless of the T cell lineage, the major histocompatibility complex haplotype, and the antigen dose. Interestingly, initiation of cell division of T cells specific for a subdominant epitope and a weak agonist was delayed by 6 h. The results provide a basis for the analysis of short range, mutual cell–cell interactions within such confined microenvironments.

Key Words: cell-cell interaction • microenvironment • T cell activation • compartmentalization • dendritic cells

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