T Cell Repertoire Scanning Is Promoted by Dynamic Dendritic Cell Behavior and Random T Cell Motility in the Lymph Node

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 4; pp. 998 - 1003
• Main Authors: Miller, Mark J., Hejazi, Arsalan S., Wei, Sindy H., Cahalan, Michael D., Parker, Ian
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27.01.2004; National Acad Sciences
• Subjects: Animals; Antigens; Atoms & subatomic particles; B lymphocytes; Biological Sciences; Cell Separation; Dendrites; Dendritic Cells - immunology; Flow Cytometry; Imaging; Immunology; Infections; Lymph nodes; Lymph Nodes - immunology; Lymphatic system; Mice; Mice, Transgenic; Microscopy; Ova; Surface areas; T cell receptors; T lymphocytes; T-Lymphocyte Subsets; Tissues
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0306407101

Dendritic cells (DCs) ingest antigens in peripheral tissues and migrate to lymph nodes where they present MHC class II-bound antigen to CD4+T cells. We used two-photon microscopy to image the single-cell dynamics of interactions between DCs and T cells within intact lymph nodes in the absence of relevant antigen. DCs were fluorescently labeled in vivo by cutaneous injection of alum adjuvant including carboxyfluorescein diacetate succinimidyl ester (CFSE). CFSE-positive DCs ($CD11c^+,\>CD11b^+$, and low-to-intermediate CD8+) were observed in draining lymph nodes 24-72 h later. Labeled DCs meandered slowly$(2-3\>\>\mu m\!\cdot\!min^{-1})$in the T cell zone near B cell follicles but vigorously extended long agile dendrites. Encounters between T cells and DCs arose as T cells moved autonomously along random paths. Moreover, T cells did not accumulate around DCs, and their relative velocities approaching and departing DCs were equivalent, implying that T cells are not attracted toward DCs by chemotactic gradients but rather encounter them by chance. T cell/DC contacts occurred primarily on dendrites at arm's length from the DC soma and typically lasted ≈3 min, enabling an individual DC to interact with up to 5,000 T cells per hour. We conclude that dynamic DC gesticulation and random T cell motility together enhance the stochastic scanning of the T cell repertoire, thereby enabling rapid initiation of the immune response.