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Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8⁺ T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A?+?D.

ABSTRACT: Previous research has evaluated antibody responses toward an influenza virus vaccine in the context of deficiencies for vitamins A and D (VAD+VDD). Results showed that antibodies and antibody-forming cells in the respiratory tract were reduced in VAD+VDD mice. However, effectors were recovered when oral supplements of vitamins A?+?D were delivered at the time of vaccination. Here we address the question of how vaccine-induced CD8⁺ T cell responses are affected by deficiencies for vitamins A?+?D. VAD+VDD and control mice were vaccinated with an intranasal, cold-adapted influenza virus A/Puerto Rico/8/34 vaccine, with or without oral supplements of vitamins A?+?D. Results showed that the percentages of vaccine-induced CD8⁺ T cell and total CD4⁺ T cell responses were low among lymphocytes in the airways of VAD+VDD animals compared to controls. The CD103 membrane marker, a protein that binds e-cadherin (expressed on respiratory tract epithelial cells), was unusually high on virus-specific T cells in VAD+VDD mice compared to controls. Interestingly, when T cells specific for the PA_224-233/D^b epitope were compared with T cells specific for the NP_366-374/D^b epitope, the former population was more strongly positive for CD103. Preliminary experiments revealed normal or above-normal percentages for vaccine-induced T cells in airways when VAD+VDD animals were supplemented with vitamins A?+?D at the time of vaccination and on days 3 and 7 after vaccination. Our results suggest that close attention should be paid to levels of vitamins A and D among vaccine recipients in the clinical arena, as low vitamin levels may render individuals poorly responsive to vaccines.

SUBMITTER: Surman SL

PROVIDER: S-EPMC5709699 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8<sup>+</sup> T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A + D.

Surman Sherri L SL Jones Bart G BG Woodland David L DL Hurwitz Julia L JL

Viral immunology 20171113 10

Previous research has evaluated antibody responses toward an influenza virus vaccine in the context of deficiencies for vitamins A and D (VAD+VDD). Results showed that antibodies and antibody-forming cells in the respiratory tract were reduced in VAD+VDD mice. However, effectors were recovered when oral supplements of vitamins A + D were delivered at the time of vaccination. Here we address the question of how vaccine-induced CD8<sup>+</sup> T cell responses are affected by deficiencies for vita ...[more]

PMID: 29130830

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Project description:PurposeImmune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8+ lymphocytes in a wide range of different cancer types and subtypes.MethodsThe density of CD8+ lymphocytes was compared across different cancer types using tissue microarrays (TMAs) composed of up to 50 tumor samples each from 84 different cancer types and subtypes. In total 2652 cancers and 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed by automated image analysis of digitized slides.ResultsWe found that the median CD8+ lymphocyte counts ranged from 6 cells/mm2 in pleomorphic adenoma up to 1573 cells/mm2 in Hodgkin's lymphoma. The CD8 counts were generally lower in normal tissues compared to cancer tissues. Blood vessels of the spleen were the only non-lymphatic tissue staining positive for CD8. Tumor types approved for checkpoint inhibitor therapy, including malignant melanoma (81), muscle invasive urothelial carcinoma (119), small cell lung cancer (120), clear cell renal cell cancer (153), squamous cell carcinoma (189) and adenocarcinoma of the lung (328) as well as Hodgkin's lymphoma (1573) were all ranking among the upper half of our list. Comparably high CD8 densities (median cells/mm2) were also found in several rare and aggressive cancer types including Merkel cell carcinoma (70), angiosarcoma (95), anaplastic thyroid cancer (156) and embryonal carcinoma of the testis (186). In 73 of the 84 analyzed cancer types, the highly variable CD8 counts occasionally exceeded the average CD8 count of tumors for which checkpoint inhibitors have been approved.ConclusionThese data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors.

Dataset Information

Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8⁺ T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A?+?D.

Publications

Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8<sup>+</sup> T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A + D.

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Dataset Information

Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8+ T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A?+?D.

Publications

Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8<sup>+</sup> T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A + D.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8⁺ T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A?+?D.