Dynamic changes during the immune response in T cell-antigen-presenting cell clusters isolated from lymph nodes.
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.
Hommel
Mirja
M
Tumor Immunology Program, Division of Cellular Immunology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Kyewski
Bruno
B
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002450:Cell Communication; D002455:Cell Division; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007114:Immunization; D016056:Immunodominant Epitopes; D066298:In Vitro Techniques; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell; D005620:Freund's Adjuvant