Regulatory CD4+CD25+ T cells restrict memory CD8+ T cell responses |
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Authors: | Kursar Mischo Bonhagen Kerstin Fensterle Joachim Köhler Anne Hurwitz Robert Kamradt Thomas Kaufmann Stefan H E Mittrücker Hans-Willi |
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Affiliation: | Max Planck Institute for Infection Biology, Department of Immunology. Deutsches Rheumaforschungszentrum, Schumannstr. 21/22, 10117 Berlin, Germany. |
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Abstract: | 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. |
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Keywords: | T lymphocytes memory bacterial infection regulation vaccination |
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