Regulatory CD4+CD25+ T cells restrict memory CD8+ T cell responses.
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.
Kursar
Mischo
M
Max Planck Institute for Infection Biology, Department of Immunology. Deutsches Rheumaforschungszentrum, Schumannstr. 21/22, 10117 Berlin, Germany.
Bonhagen
Kerstin
K
Fensterle
Joachim
J
Köhler
Anne
A
Hurwitz
Robert
R
Kamradt
Thomas
T
Kaufmann
Stefan H E
SH
Mittrücker
Hans-Willi
HW
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010455:Peptides / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology
D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D010455:Peptides; D015375:Receptors, Interleukin-2; D019444:Vaccines, DNA