Single-cell analysis of signal transduction in CD4 T cells stimulated by antigen in vivo.
Flow cytometry was used to study signaling events in individual CD4 T cells after antigen recognition in the body. Phosphorylation of c-jun and p38 mitogen-activated protein kinase was detected within minutes in all antigen-specific CD4 T cells in secondary lymphoid tissues after injection of peptide antigen into the bloodstream. The remarkable rapidity of this response correlated with the finding that most naive T cells are in constant contact with dendritic antigen-presenting cells. Contrary to predictions from in vitro experiments, antigen-induced c-jun and p38 mitogen-activated protein kinase phosphorylation did not depend on CD28 signals and was insensitive to inhibition by cyclosporin A. Our results highlight the efficiency of the in vivo immune response and underscore the need to verify which signaling pathways identified in vitro actually operate under physiological conditions.
Zell
T
T
Department of Microbiology, University of Minnesota, Minneapolis, MN 55455, USA.
Khoruts
A
A
Ingulli
E
E
Bonnevier
J L
JL
Mueller
D L
DL
Jenkins
M K
MK
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D018106:CD28 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004789:Enzyme Activation; D005434:Flow Cytometry / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D000941:Antigens; D018106:CD28 Antigens; D007166:Immunosuppressive Agents; D016755:Proto-Oncogene Proteins c-jun; D016572:Cyclosporine; D010047:Ovalbumin; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases