Priming of CD8+ and CD4+ T cells in experimental leishmaniasis is initiated by different dendritic cell subtypes.
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Priming of CD8+ and CD4+ T cells in experimental leishmaniasis is initiated by different dendritic cell subtypes. / Brewig, Nancy; Kissenpfennig, Adrien; Malissen, Bernard; Veit, Alexandra; Bickert, Thomas; Fleischer, Bernhard; Mostböck, Sven; Ritter, Uwe.
In: J IMMUNOL, Vol. 182, No. 2, 2, 2009, p. 774-783.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Priming of CD8+ and CD4+ T cells in experimental leishmaniasis is initiated by different dendritic cell subtypes.
AU - Brewig, Nancy
AU - Kissenpfennig, Adrien
AU - Malissen, Bernard
AU - Veit, Alexandra
AU - Bickert, Thomas
AU - Fleischer, Bernhard
AU - Mostböck, Sven
AU - Ritter, Uwe
PY - 2009
Y1 - 2009
N2 - The biological role of Langerin+ dendritic cells (DCs) such as Langerhans cells and a subset of dermal DCs (dDCs) in adaptive immunity against cutaneous pathogens remains enigmatic. Thus, we analyzed the impact of Langerin+ DCs in adaptive T cell-mediated immunity toward Leishmania major parasites in a Lang-DTR mouse model that allows conditional diphtheria toxin (DT)-induced ablation of Langerin+ DCs in vivo. For the first time, infection experiments with DT-treated Lang-DTR mice revealed that proliferation of L. major-specific CD8+ T cells is significantly reduced during the early phase of the immune response following depletion of Langerin+ DCs. Consequently, the total number of activated CD8+ T cells within the draining lymph node and at the site of infection is diminished. Furthermore, we show that the impaired CD8+ T cell response is due to the absence of Langerin+ dDCs and not Langerhans cells. Nevertheless, the CD4+ T cell response is not altered and the infection is cleared as effectively in DT-treated Lang-DTR mice as in control mice. This clearly demonstrates that Langerin+ DCs are, in general, dispensable for an efficient adaptive immune response against L. major parasites. Thus, we propose a novel concept that, in the experimental model of leishmaniasis, priming of CD4+ T cells is mediated by Langerin- dDCs, whereas Langerin+ dDCs are involved in early priming of CD8+ T cells.
AB - The biological role of Langerin+ dendritic cells (DCs) such as Langerhans cells and a subset of dermal DCs (dDCs) in adaptive immunity against cutaneous pathogens remains enigmatic. Thus, we analyzed the impact of Langerin+ DCs in adaptive T cell-mediated immunity toward Leishmania major parasites in a Lang-DTR mouse model that allows conditional diphtheria toxin (DT)-induced ablation of Langerin+ DCs in vivo. For the first time, infection experiments with DT-treated Lang-DTR mice revealed that proliferation of L. major-specific CD8+ T cells is significantly reduced during the early phase of the immune response following depletion of Langerin+ DCs. Consequently, the total number of activated CD8+ T cells within the draining lymph node and at the site of infection is diminished. Furthermore, we show that the impaired CD8+ T cell response is due to the absence of Langerin+ dDCs and not Langerhans cells. Nevertheless, the CD4+ T cell response is not altered and the infection is cleared as effectively in DT-treated Lang-DTR mice as in control mice. This clearly demonstrates that Langerin+ DCs are, in general, dispensable for an efficient adaptive immune response against L. major parasites. Thus, we propose a novel concept that, in the experimental model of leishmaniasis, priming of CD4+ T cells is mediated by Langerin- dDCs, whereas Langerin+ dDCs are involved in early priming of CD8+ T cells.
M3 - SCORING: Zeitschriftenaufsatz
VL - 182
SP - 774
EP - 783
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 2
M1 - 2
ER -
