CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses
Rosa Varona, … , Carlos Martínez-A., Gabriel Márquez
Rosa Varona, … , Carlos Martínez-A., Gabriel Márquez
Published March 15, 2001
Citation Information: J Clin Invest. 2001;107(6):R37-R45. https://doi.org/10.1172/JCI11297.
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CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses

Abstract

CCR6 expression in dendritic, T, and B cells suggests that this β-chemokine receptor may regulate the migration and recruitment of antigen-presenting and immunocompetent cells during inflammatory and immunological responses. Here we demonstrate that CCR6–/– mice have underdeveloped Peyer’s patches, in which the myeloid CD11b+ CD11c+ dendritic-cell subset is not present in the subepithelial dome. CCR6–/– mice also have increased numbers in T-cell subpopulations within the intestinal mucosa. In 2,4-dinitrofluorobenzene–induced contact hypersensitivity (CHS) studies, CCR6–/– mice developed more severe and more persistent inflammation than wild-type (WT) animals. Conversely, in a delayed-type hypersensitivity (DTH) model induced with allogeneic splenocytes, CCR6–/– mice developed no inflammatory response. The altered responses seen in the CHS and DTH assays suggest the existence of a defect in the activation and/or migration of the CD4+ T-cell subsets that downregulate or elicit the inflammation response, respectively. These findings underscore the role of CCR6 in cutaneous and intestinal immunity and the utility of CCR6–/– mice as a model to study pathologies in these tissues.

Authors

Rosa Varona, Ricardo Villares, Laura Carramolino, Íñigo Goya, Ángel Zaballos, Julio Gutiérrez, Miguel Torres, Carlos Martínez-A., Gabriel Márquez

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CCR6–/– mice have a markedly diminished DTH response to allogeneic BALB/...
CCR6–/– mice have a markedly diminished DTH response to allogeneic BALB/c splenocytes. (a) CCR6–/– (n = 10; circles) and CCR6+/+ (n = 11; squares) animals were sensitized by intravenous injection of 106 BALB/c splenocytes. Five days later, mice were challenged by injecting 13 × 106 BALB/c splenocytes into their right footpads, and swelling was measured 24 hours later. Individual data and the mean value for each group are presented. The two-tailed t-test value for these data was P = 0.000016. (b) In vitro MLR to allogeneic BALB/c splenocytes. Lymphocytes were prepared from IAB LNs from CCR6+/+ (filled squares) and CCR6–/– mice (filled circles) and cultured in 96-well plates (2 × 105 cells/well) with increasing amounts of stimulator allogeneic BALB/c splenocytes. After 72 hours, cultures were pulsed with 3H-thymidine for 24 hours and cell proliferation was estimated. Background proliferation is also shown (open symbols). Each point represents the average value of two separate groups, each consisting of pooled LNs from two mice. Assays were performed in triplicate. (c) Adoptive transfer of sensitized CCR6+/+ CD4+ T cells to CCR6–/– mice restores their ability to produce a DTH response. Unsensitized CCR6+/+ and CCR6–/– mice were adoptively transferred with 2 × 107 CD4+ T cell–enriched preparations purified from sensitized CCR6+/+ and CCR6–/– donors, as indicated. T cells from CCR6–/– IAB LNs were also allowed to proliferate in an in vitro MLR assay with BALB/c splenocytes before being injected to CCR6–/– hosts (++). After 16 hours, animals were challenged with 13 × 106 BALB/c splenocytes in footpads, and swelling was measured 24 hours later.