Ca2+ signals in CD4+ T cells during early contacts with antigen-bearing dendritic cells in lymph node.
T cell activation by APC requires cytosolic Ca(2+) ([Ca(2+)](i)) elevation. Using two-photon microscopy, we visualized Ca(2+) signaling and motility of murine CD4(+) T cells within lymph node (LN) explants under control, inflammatory, and immunizing conditions. Without Ag under basal noninflammatory conditions, T cells showed infrequent Ca(2+) spikes associated with sustained slowing. Inflammation reduced velocities and Ca(2+) spiking in the absence of specific Ag. During early Ag encounter, most T cells engaged Ag-presenting dendritic cells in clusters, and showed increased Ca(2+) spike frequency and elevated basal [Ca(2+)](i). These Ca(2+) signals persisted for hours, irrespective of whether T cells were in contact with visualized dendritic cells. We propose that sustained increases in basal [Ca(2+)](i) and spiking frequency constitute a Ca(2+) signaling modality that, integrated over hours, distinguishes immunogenic from basal state in the native lymphoid environment.
Wei
Sindy H
SH
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.
Safrina
Olga
O
Yu
Ying
Y
Garrod
Kym R
KR
Cahalan
Michael D
MD
Parker
Ian
I
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D020013:Calcium Signaling / Q000276:immunology*; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000502:physiology*; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D018836:Inflammation Mediators / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D018836:Inflammation Mediators; C111390:OVA 323-339; D010446:Peptide Fragments; D010047:Ovalbumin