TY - JOUR
T1 - Dendritic cell-derived IL-15 controls the induction of CD8 T cell immune reponses
AU - Rückert, René
AU - Brandt, Katja
AU - Bulanova, Elena
AU - Mirghomizadeh, Farhad
AU - Paus, Ralf
AU - Bulfone-Paus, Silvia
PY - 2003/12
Y1 - 2003/12
N2 - The development and the differentiation of CD8+ T cells are dependent on IL-15. Here, we have studied the source and mechanism of how IL-15 modulates CD8+ T cell-mediated Th1 immune responses by employing two delayed-type hypersensitivity (DTH) models. IL-15-deficient (IL-15-/-) mice or mice treated with soluble IL-15Rα as an IL-15 antagonist showed significantly reduced CD8+ T cell-dependent DTH responses, while activation of CD4+ T cell and B cell functions remained unaffected. Injection of antigen-labeled dendritic cells (DC) from IL-15+/+, IL-15-/- or IL-15Rα-/- mice revealed that DC-derived IL-15 is an absolute requirement for the initiation of DTH response. The re-establishment of the interaction of IL-15 with the IL-15Rα by incubating IL-15-/- DC with IL-15 completely restored the capacity to prime T cells for DTH induction in vivo. Moreover, IL-15 also enhanced secretion of proinflammatory cytokines by DC and triggered in vitro CD8+ T cell proliferation and IL-2 release. Taken together, the data suggest that an autocrine IL-15/IL-15Rα signaling loop in DC is essential for inducing CD8+-dependent Th1 immune responses in mice. Therefore, targeted manipulation of this loop promises to be an effective, novel strategy for therapeutic modulation of clinically relevant DTH reactions.
AB - The development and the differentiation of CD8+ T cells are dependent on IL-15. Here, we have studied the source and mechanism of how IL-15 modulates CD8+ T cell-mediated Th1 immune responses by employing two delayed-type hypersensitivity (DTH) models. IL-15-deficient (IL-15-/-) mice or mice treated with soluble IL-15Rα as an IL-15 antagonist showed significantly reduced CD8+ T cell-dependent DTH responses, while activation of CD4+ T cell and B cell functions remained unaffected. Injection of antigen-labeled dendritic cells (DC) from IL-15+/+, IL-15-/- or IL-15Rα-/- mice revealed that DC-derived IL-15 is an absolute requirement for the initiation of DTH response. The re-establishment of the interaction of IL-15 with the IL-15Rα by incubating IL-15-/- DC with IL-15 completely restored the capacity to prime T cells for DTH induction in vivo. Moreover, IL-15 also enhanced secretion of proinflammatory cytokines by DC and triggered in vitro CD8+ T cell proliferation and IL-2 release. Taken together, the data suggest that an autocrine IL-15/IL-15Rα signaling loop in DC is essential for inducing CD8+-dependent Th1 immune responses in mice. Therefore, targeted manipulation of this loop promises to be an effective, novel strategy for therapeutic modulation of clinically relevant DTH reactions.
KW - Cytokines
KW - Dendritic cells
KW - Inflammation
KW - Rodent
U2 - 10.1002/eji.200324545
DO - 10.1002/eji.200324545
M3 - Article
C2 - 14635060
SN - 1521-4141
VL - 33
SP - 3493
EP - 3503
JO - European journal of immunology
JF - European journal of immunology
IS - 12
ER -