Human epidermal Langerhans' cells are targets for the immunosuppressive macrolide tacrolimus (FK506) Andrea Panhans-Groß, MD, Natalija Novak, MD, Stefan.

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Presentation transcript:

Human epidermal Langerhans' cells are targets for the immunosuppressive macrolide tacrolimus (FK506) Andrea Panhans-Groß, MD, Natalija Novak, MD, Stefan Kraft, MD, Thomas Bieber, MD, PhD Journal of Allergy and Clinical Immunology Volume 107, Issue 2, Pages 345-352 (February 2001) DOI: 10.1067/mai.2001.112600 Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 1 FKBP12 is expressed in freshly isolated LCs but lost during in vitro maturation with GM-CSF. A, Double-labeling with anti-FKBP12 and anti-CD1a was performed either directly after isolation (upper panel) and at 36 hours (lower panel). The black profile represents the respective isotype control, and the blue profile represents the FKBP12 expression. Data representative from a series of 3 experiments are shown. B, Kinetics of the FKBP12 expression in epidermal LCs. Journal of Allergy and Clinical Immunology 2001 107, 345-352DOI: (10.1067/mai.2001.112600) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 2 Tacrolimus and βMv affect the expression of MHC I and II on in vitro maturated epidermal LCs. The expression of MHC I (A) and MHC II (B) was analyzed by double-labeling and flow cytometry. The results show the data for the optimal concentrations of tacrolimus (10–8 mol/L) (circles, red graph) and βMv (10–7 mol/L) (triangles, green graph) and are expressed as the percentage of positive LCs for MHC I on the y-axis of A and relative fluorescence intensity for MHC II on the y-axis of B (mean ± SEM; n = 3). Journal of Allergy and Clinical Immunology 2001 107, 345-352DOI: (10.1067/mai.2001.112600) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 3 Differential effect of tacrolimus (circles, red graph) and βMv (triangles, green graph) on costimulatory molecules on LCs. Freshly isolated LCs were cultured and analyzed for the expression of CD80 (A), CD86 (B), and CD40 (C) as described above. Data are expressed as the percentage of positive LCs (mean ± SEM; n = 5). Journal of Allergy and Clinical Immunology 2001 107, 345-352DOI: (10.1067/mai.2001.112600) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 4 Tacrolimus inhibits CD25 expression on LCs, whereas βMv clearly upregulates its emergence. Cells were then double-labeled with an anti-CD25 mAb and anti-CD1a mAb. Results are expressed as the percentage of positive LCs (mean ± SEM; n = 5). Journal of Allergy and Clinical Immunology 2001 107, 345-352DOI: (10.1067/mai.2001.112600) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 5 Tacrolimus and βMv impair the allostimulatory activity of cultured LCs. A, A stimulator cell. Results are expressed as the percentage of stimulation relative to the control (ie, untreated) ECs (mean ± SEM; n = 5). B, After 36 hours, untreated crude ECs (T+EC), tacrolimus-treated crude ECs (T+EC+FK), untreated LC-depleted ECs (T+depl.EC), a 1:1 mixture of untreated LC-depleted ECs and untreated crude ECs (T+depl.EC+EC), and a 1:1 mixture of tacrolimus-treated LC-depleted ECs and untreated crude ECs (T+depl.EC(FK)+EC). Subsequently, cell proliferation was measured. Results are expressed as the percentage of stimulation relative to the control (ie, untreated) ECs (mean ± SEM; n = 4). Journal of Allergy and Clinical Immunology 2001 107, 345-352DOI: (10.1067/mai.2001.112600) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 6 Schema to summarize the cellular and molecular mechanisms of tacrolimus. stim. capacity, Stimulatory capacity toward T cells in the allogeneic mixed lymphocyte reaction. Arbitrary units: –, absent; +, weak to moderate; ++, strong; and +++, very strong. Journal of Allergy and Clinical Immunology 2001 107, 345-352DOI: (10.1067/mai.2001.112600) Copyright © 2001 Mosby, Inc. Terms and Conditions