The Journal of Experimental Medicine
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Published online 14 August 2006 doi:10.1084/jem.20060928
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 9, 2135-2143
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ARTICLE

 Duration of the initial TCR stimulus controls the magnitude but not functionality of the CD8+ T cell response

Martin Prlic, Gabriela Hernandez-Hoyos, and Michael J. Bevan

Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195

CORRESPONDENCE Michael J. Bevan: mbevan{at}u.washington.edu

CD8+ T cells only require a brief stimulation with antigen in vitro to divide and differentiate into effector and memory cells upon transfer in vivo. The efficiency of clonal expansion and the functional characteristics of memory cells derived from briefly stimulated cells are poorly defined. We developed a system that allowed us to examine programming entirely in vivo. This was achieved by rapidly killing peptide-pulsed DCs carrying a diphtheria toxin receptor transgene with timed injections of diphtheria toxin without altering the course of an accompanying infection. The magnitude of clonal expansion, but not the functionality of the effector cells, correlated directly with the duration of antigen exposure. Furthermore, memory T cells were capable of mounting a secondary response, regardless of the length of antigen encounter during the primary response. These results indicate that the duration of initial antigen encounter influences the magnitude of the primary response, but does not program responsiveness during the secondary challenge.

Abbreviations used: DT, diptheria toxin; DTR, DT receptor; DTRtg, DTR transgene.

G. Hernandez-Hoyos' present address is ZymoGenetics, Seattle, WA 98102.


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