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Lehmann, Christian H. K.; Baranska, Anna; Heidkamp, Gordon F.; Heger, Lukas; Neubert, Kirsten; Lühr, Jennifer J.; Hoffmann, Alana; Reimer, Katharina C.; Brückner, Christin; Beck, Simone; Seeling, Michaela; Kiessling, Melissa; Soulat, Didier; Krug, Anne B.; Ravetch, Jeffrey V.; Leusen, Jeanette H. W.; Nimmerjahn, Falk; Dudziak, Diana (2017): DC subset-specific induction of T cell responses upon antigen uptake via Fc gamma receptors in vivo. In: Journal of Experimental Medicine, Vol. 214, No. 5: pp. 1509-1528
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Abstract

Dendritic cells (DCs) are efficient antigen-presenting cells equipped with various cell surface receptors for the direct or indirect recognition of pathogenic microorganisms. Interestingly, not much is known about the specific expression pattern and function of the individual activating and inhibitory Fc gamma receptors (Fc gamma Rs) on splenic DC subsets in vivo and how they contribute to the initiation of T cell responses. By targeting antigens to select activating and the inhibitory Fc gamma R in vivo, we show that antigen uptake under steady-state conditions results in a short-term expansion of antigen-specific T cells, whereas under inflammatory conditions especially, the activating Fc gamma RIV is able to induce superior CD4(+) and CD8(+) T cell responses. Of note, this effect was independent of Fc gamma R intrinsic activating signaling pathways. Moreover, despite the expression of Fc gamma RIV on both conventional splenic DC subsets, the induction of CD8(+) T cell responses was largely dependent on CD11c(+) CD8(+) DCs, whereas CD11c(+) CD8-DCs were critical for priming CD4(+) T cell responses.