Single-cell analysis of signal transduction in CD4 T cells stimulated by antigen in vivo

Traci Zell, Alexander Khoruts, Elizabeth Ingulli, Jody L. Bonnevier, Daniel L. Mueller, Marc K. Jenkins

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


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 mitogenactivated 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.

Original languageEnglish (US)
Pages (from-to)10805-10810
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number19
StatePublished - Sep 11 2001


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