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CCR5 Usage by CCL5 Induces a Selective Leukocyte Recruitment in Human Skin Xenografts In Vivo  Patricia de Nadaï, Cécile Chenivesse, Jules Gilet, Henri.

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Presentation on theme: "CCR5 Usage by CCL5 Induces a Selective Leukocyte Recruitment in Human Skin Xenografts In Vivo  Patricia de Nadaï, Cécile Chenivesse, Jules Gilet, Henri."— Presentation transcript:

1 CCR5 Usage by CCL5 Induces a Selective Leukocyte Recruitment in Human Skin Xenografts In Vivo 
Patricia de Nadaï, Cécile Chenivesse, Jules Gilet, Henri Porte, Han Vorng, Ying Chang, Andrew F. Walls, Benoît Wallaert, André- Bernard Tonnel, Anne Tsicopoulos, Hans-Günter Zerwes  Journal of Investigative Dermatology  Volume 126, Issue 9, Pages (September 2006) DOI: /sj.jid Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Inhibitory effects of neutralizing anti-CCR5 antibody on human PBMC and murine eosinophil chemotaxis in vitro. (a) Dose-dependent inhibitory effect of CCR5-blocking antibody on human PBMC chemotaxis. Activated human PBMC were incubated with increasing concentrations of anti-CCR5 or IgG2a antibodies, and chemoattracted by CCL5. Results are expressed as the percentage of inhibition of PBMC migration. (b) Functional chemotactic cross-reactivity between anti-human CCR5 and murine eosinophils. Eosinophils from IL-5 transgenic mice were incubated with 10μg/ml of anti-CCR5 or control IgG2a antibodies and chemoattracted using human CCL5. Results are expressed as means±SEM number of recruited eosinophils per field (n=3). Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 Effect of anti-CCR5 treatment on CCL5-induced skin xenograft lymphocyte infiltration. Infiltration of human CD45+ leukocytes, CD4+ T cells, IL-2R CD25+ T cells, and CD45RO+ memory T cells, following CCL-5 versus diluent challenges in 26 skin grafts obtained from normal donors, 24hours after intravenous antibody injection and intraperitoneal introduction of IgG2a- or anti-CCR5-treated autologous human PBMC. Results are expressed as the number of positive cells per mm2. Median values are represented by the solid bars. Differences within the four groups were first evaluated by using the Kruskal–Wallis test and were found statistically significant for the four markers. Comparisons within CCL5 and diluent values were performed by using the Wilcoxon test. Comparisons between IgG2a and anti-CCR5-treated groups were performed by using the Mann–Whitney U-test after subtraction of the diluent values from CCL5 values. P-values as indicated, NS: not significant. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 Effect of anti-CCR5 treatment on CCL5-induced skin xenograft leukocyte infiltration. Infiltration of human CD68+ monocytes/macrophages, CD1a+ immature DCs, BB1+ basophils, and murine MBP+ eosinophils, following CCL-5 versus diluent challenges as described in Figure 2. Results are expressed as in Figure 2. Kruskal–Wallis test was not significant for CD1a+ and BB1+ cell infiltration. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 Effect of anti-CCR5 treatment on CCL5-induced skin xenograft cytokine-expressing cell infiltration. Infiltration of human Th1 and Th2 cytokine-expressing cells, following CCL-5 versus diluent challenges as described in Figure 2. Results are expressed as in Figure 2. Kruskal–Wallis test was only significant for IFN-γ+ cell infiltration. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

6 Figure 5 Immunostaining of cryostat sections of human skin grafts. Anti-CD68 staining of CCL5-injected skin grafts in SCID mice treated with (a) IgG2a (Bar=50μm) or (b) anti-CCR5 (Bar=50μm) antibody. Anti-IFN-γ staining of CCL5-injected skin grafts in SCID mice treated with (c) IgG2a (Bar=25μm) or (d) anti-CCR5 (Bar=25μm) antibody. Immunostaining was performed by using the alkaline phosphatase antialkaline phosphatase technique. Journal of Investigative Dermatology  , DOI: ( /sj.jid ) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

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