The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online 9 December 2002 doi:10.1084/jem.20011347
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© Rockefeller University Press, 0022-1007/2002/12/1585/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 12, December 16, 2002 1585-1592

Regulatory CD4+CD25+ T Cells Restrict Memory CD8+ T Cell Responses

Mischo Kursar1, Kerstin Bonhagen2, Joachim Fensterle1, Anne Köhler1, Robert Hurwitz1, Thomas Kamradt2, Stefan H.E. Kaufmann1 and Hans-Willi Mittrücker1

1 Max Planck Institute for Infection Biology, Department of Immunology
2 Deutsches Rheumaforschungszentrum, Schumannstr. 21/22, 10117 Berlin, Germany

Address correspondence to Hans-Willi Mittrücker, Max Planck Institute for Infection Biology, Schumannstr. 21/22, 10117 Berlin, Germany. Phone: 49-30-28460-532; Fax: 49-30-28460-501; E-mail: mittruecker{at}mpiib-berlin.mpg.de

CD4+ T cell help is important for the generation of CD8+ T cell responses. We used depleting anti-CD4 mAb to analyze the role of CD4+ T cells for memory CD8+ T cell responses after secondary infection of mice with the intracellular bacterium Listeria monocytogenes, or after boost immunization by specific peptide or DNA vaccination. Surprisingly, anti-CD4 mAb treatment during secondary CD8+ T cell responses markedly enlarged the population size of antigen-specific CD8+ T cells. After boost immunization with peptide or DNA, this effect was particularly profound, and antigen-specific CD8+ T cell populations were enlarged at least 10-fold. In terms of cytokine production and cytotoxicity, the enlarged CD8+ T cell population consisted of functional effector T cells. In depletion and transfer experiments, the suppressive function could be ascribed to CD4+CD25+ T cells. Our results demonstrate that CD4+ T cells control the CD8+ T cell response in two directions. Initially, they promote the generation of a CD8+ T cell responses and later they restrain the strength of the CD8+ T cell memory response. Down-modulation of CD8+ T cell responses during infection could prevent harmful consequences after eradication of the pathogen.

Key Words: T lymphocytes • memory • bacterial infection • regulation • vaccination


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