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PNAS 98 (19): 10805-10810

Copyright © 2001 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / IMMUNOLOGY

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

Traci Zell*,{dagger},{ddagger}, Alexander Khoruts{dagger},{ddagger},§, Elizabeth Ingulli{dagger},¶, Jody L. Bonnevier{dagger},¶, Daniel L. Mueller{dagger},§, and Marc K. Jenkins*,{dagger},||

Departments of *Microbiology, §Medicine, and Pediatrics, and the {dagger}Center for Immunology, University of Minnesota, Minneapolis, MN 55455

Received for publication November 30, 2000.

Abstract: 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.

{ddagger} T.Z. and A.K. contributed equally to this work.

|| To whom reprint requests should be addressed. E-mail: marcj{at}mail.ahc.umn.edu.

Edited by James P. Allison, University of California, Berkeley, CA, and approved July 23, 2001

This paper was submitted directly (Track II) to the PNAS office.

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