PMID- 14722354 OWN - NLM STAT- MEDLINE DCOM- 20040330 LR - 20210102 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 101 IP - 4 DP - 2004 Jan 27 TI - T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node. PG - 998-1003 AB - 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 microm x 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 approximately 3 min, enabling an individual DC to interact with up to 5000 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. FAU - Miller, Mark J AU - Miller MJ AD - Department of Physiology and Biophysics , University of California, Irvine, CA 92697, USA. FAU - Hejazi, Arsalan S AU - Hejazi AS FAU - Wei, Sindy H AU - Wei SH FAU - Cahalan, Michael D AU - Cahalan MD FAU - Parker, Ian AU - Parker I LA - eng GR - GM-41514/GM/NIGMS NIH HHS/United States GR - R01 GM048071/GM/NIGMS NIH HHS/United States GR - R37 GM048071/GM/NIGMS NIH HHS/United States GR - GM-48071/GM/NIGMS NIH HHS/United States GR - R01 GM041514/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20040113 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 SB - IM MH - Animals MH - Cell Separation MH - Dendritic Cells/*immunology MH - Flow Cytometry MH - Lymph Nodes/*immunology MH - Mice MH - Mice, Transgenic MH - *T-Lymphocyte Subsets PMC - PMC327133 EDAT- 2004/01/15 05:00 MHDA- 2004/03/31 05:00 PMCR- 2004/07/27 CRDT- 2004/01/15 05:00 PHST- 2004/01/15 05:00 [pubmed] PHST- 2004/03/31 05:00 [medline] PHST- 2004/01/15 05:00 [entrez] PHST- 2004/07/27 00:00 [pmc-release] AID - 0306407101 [pii] AID - 1010998 [pii] AID - 10.1073/pnas.0306407101 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2004 Jan 27;101(4):998-1003. doi: 10.1073/pnas.0306407101. Epub 2004 Jan 13.