Type II Collagen Induces Peripheral Tolerance in BALB/c Mice via the Generation of CD8+ T Regulatory Cells
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{"title"=>"Type II Collagen Induces Peripheral Tolerance in BALB/c Mice via the Generation of CD8+ T Regulatory Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Shukkur M.", "last_name"=>"Farooq", "scopus_author_id"=>"7004833060"}, {"first_name"=>"Hossam M.", "last_name"=>"Ashour", "scopus_author_id"=>"56260407900"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"365979082", "sgr"=>"84868318180", "issn"=>"19326203", "pmid"=>"23133648", "scopus"=>"2-s2.0-84868318180", "doi"=>"10.1371/journal.pone.0048635"}, "id"=>"14e02081-850c-351e-ad8b-367d739a8bbc", "abstract"=>"Antigens introduced into the anterior chamber (AC) of the eye induce a potent form of antigen-specific peripheral immune tolerance termed AC-associated immune deviation (ACAID), which prevents inflammatory immune responses and is characterized by impaired delayed-type hypersensitivity (DTH) responses. Type-II collagen (CII) is a fibrillar protein expressed exclusively in cartilage tissues. Although of its clinical relevance to Rheumatoid arthritis, aging, and osteoarthritis, there have been no studies to date to test if CII has the ability to induce ACAID. We hypothesized that ACAID could be generated via AC injection of CII in BALB/c mice. Using a DTH assay, the hypothesis was supported and led to another hypothesis that CII is capable of inducing specific immune tolerance via CD8(+) T regulatory cells (Tregs). Thus, we performed functional local adoptive transfer (LAT) assays to examine the regulatory roles of spleen cells, T cells, and CD8(+) T cells in the specific immune regulation induced by CII injection into the AC. Results indicated that CII induced ACAID when injected into the AC. Spleen cells of mice injected with CII in the AC significantly suppressed DTH responses. The T cell compartment of the spleen was capable of expressing this suppression. CD8(+) Tregs could solely express this CII-driven suppression and even exerted more noticeable suppression than spleen cells or splenic T cells. This study suggests a crucial role for CD8(+) Tregs in mediating CII-driven ACAID-mediated immune tolerance. This could have therapeutic implications in Rheumatoid arthritis, aging, osteoarthritis, and other diseases in which CII is involved.", "link"=>"http://www.mendeley.com/research/type-ii-collagen-induces-peripheral-tolerance-balbc-mice-via-generation-cd8-t-regulatory-cells", "reader_count"=>12, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Environmental Science"=>1, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>1, "Business, Management and Accounting"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Turkey"=>1, "Brazil"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/549124"], "description"=>"<p>A LAT assay was performed as described in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048635#s2\" target=\"_blank\">materials and methods</a> section. Seven days after AC injection, mice were s.c. immunized with CII/CFA. On day 14, putative regulatory spleen cells were isolated and mixed with immune spleen cells (isolated from s.c. immunized mice) and 500 µg CII before injection into the left ear pinna of naïve mice. Positive control mice received immune and naïve spleen cells along with CII. Two negative controls were included; one received only naïve spleen cells along with CII and the other received only CII. The regulatory activity of spleen cells was confirmed by inhibition of ear swelling responses induced by immune spleen cells after 24 hr (panel ‘a’) and 48 hr (panel ‘b’).</p>", "links"=>[], "tags"=>["spleen", "cells", "cii", "injected", "inhibit", "cii-induced", "dth", "responses", "mice"], "article_id"=>219613, "categories"=>["Biochemistry", "Immunology"], "users"=>["Shukkur M. Farooq", "Hossam M. Ashour"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0048635.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_generated_spleen_cells_as_a_result_of_CII_injected_in_the_AC_inhibit_CII_induced_DTH_responses_in_BALB_c_mice_LAT_assay_/219613", "title"=>"<i>In vivo</i>-generated spleen cells (as a result of CII injected in the AC) inhibit CII-induced DTH responses in BALB/c mice (LAT assay).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:52:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/549004"], "description"=>"<p><b>(DTH assay).</b> A DTH assay was performed as described in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048635#s2\" target=\"_blank\">materials and methods</a> section. To induce ACAID, mice received an AC injection of CII followed by immunization (s.c.) on day 7 with CII/CFA. On day 14, mice were challenged with CII (500 µg in 20 µl) intradermally in the left ear pinna, and 20 µl PBS alone was injected into the right ear pinna as an internal control. Induction of ACAID was confirmed by inhibition of ear-swelling responses after 24 hr (panel ‘a’) and 48 hr (panel ‘b’). The positive control mice were immunized s.c. with CII/CFA on day 7 and with CII on day 14 whereas the negative control mice only received the day 14 intradermal injection of CII.</p>", "links"=>[], "tags"=>["injection", "cii", "induced", "acaid", "mice", "suppression"], "article_id"=>219492, "categories"=>["Biochemistry", "Immunology"], "users"=>["Shukkur M. Farooq", "Hossam M. Ashour"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0048635.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AC_injection_of_CII_induced_ACAID_in_BALB_c_mice_via_the_suppression_of_DTH_/219492", "title"=>"AC injection of CII induced ACAID in BALB/c mice via the suppression of DTH", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:51:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/549392"], "description"=>"<p>A LAT assay was performed as described in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048635#s2\" target=\"_blank\">materials and methods</a> section. Seven days after AC injection, mice were s.c. immunized with CII/CFA. On day 14, putative regulatory splenic CD8<sup>+</sup> T cells were isolated (CD8<sup>+</sup> microBeads) and mixed with immune spleen cells (isolated from s.c. immunized mice) and 500 µg CII before injection into the left ear pinna of naïve mice. Positive control mice received immune and naïve spleen cells along with CII. Two negative controls were included; one received only naïve spleen cells along with CII and the other received only CII. The regulatory activity of splenic CD8<sup>+</sup> T cells was confirmed by inhibition of ear swelling responses induced by immune spleen cells after 24 hr (panel ‘a’) and 48 hr (panel ‘b’).</p>", "links"=>[], "tags"=>["splenic", "cells", "cii", "injected", "inhibit", "cii-induced", "dth", "responses", "mice"], "article_id"=>219881, "categories"=>["Biochemistry", "Immunology"], "users"=>["Shukkur M. Farooq", "Hossam M. Ashour"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0048635.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_generated_splenic_CD8_T_cells_as_a_result_of_CII_injected_in_the_AC_inhibit_CII_induced_DTH_responses_in_BALB_c_mice_LAT_assay_/219881", "title"=>"<i>In vivo</i>-generated splenic CD8<sup>+</sup> T cells (as a result of CII injected in the AC) inhibit CII-induced DTH responses in BALB/c mice (LAT assay).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:53:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/549255"], "description"=>"<p>A LAT assay was performed as described in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048635#s2\" target=\"_blank\">materials and methods</a> section. Seven days after AC injection, mice were s.c. immunized with CII/CFA. On day 14, putative regulatory splenic T cells were isolated (CD90.2 microBeads) and mixed with immune spleen cells (isolated from s.c. immunized mice) and 500 µg CII before injection into the left ear pinna of naïve mice. Positive control mice received immune and naïve spleen cells along with CII. Two negative controls were included; one received only naïve spleen cells along with CII and the other received only CII. The regulatory activity of splenic T cells was confirmed by inhibition of ear swelling responses induced by immune spleen cells after 24 hr (panel ‘a’) and 48 hr (panel ‘b’).</p>", "links"=>[], "tags"=>["splenic", "cells", "cii", "injected", "inhibit", "cii-induced", "dth", "responses", "mice"], "article_id"=>219746, "categories"=>["Biochemistry", "Immunology"], "users"=>["Shukkur M. Farooq", "Hossam M. Ashour"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0048635.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_generated_splenic_T_cells_as_a_result_of_CII_injected_in_the_AC_inhibit_CII_induced_DTH_responses_in_BALB_c_mice_LAT_assay_/219746", "title"=>"<i>In vivo</i>-generated splenic T cells (as a result of CII injected in the AC) inhibit CII-induced DTH responses in BALB/c mice (LAT assay).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:52:59"}

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Relative Metric

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