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Suppression of Chlamydial Pathogenicity by Nonspecific CD8⁺ T Lymphocytes.

ABSTRACT: Chlamydia trachomatis, a leading infectious cause of tubal infertility, induces upper genital tract pathology, such as hydrosalpinx, which can be modeled with Chlamydia muridarum infection in mice. Following C. muridarum inoculation, wild-type mice develop robust hydrosalpinx, but OT1 mice fail to do so because their T cell receptors are engineered to recognize a single ovalbumin epitope (OVA_457-462). These observations have demonstrated a critical role of Chlamydia-specific T cells in chlamydial pathogenicity. In the current study, we have also found that OT1 mice can actively inhibit chlamydial pathogenicity. First, depletion of CD8⁺ T cells from OT1 mice led to the induction of significant hydrosalpinx by Chlamydia, indicating that CD8⁺ T cells are necessary to inhibit chlamydial pathogenicity. Second, adoptive transfer of CD8⁺ T cells from OT1 mice to CD8 knockout mice significantly reduced chlamydial induction of hydrosalpinx, demonstrating that OT1 CD8⁺ T cells are sufficient for attenuating chlamydial pathogenicity in CD8 knockout mice. Finally, CD8⁺ T cells from OT1 mice also significantly inhibited hydrosalpinx development in wild-type mice following an intravaginal inoculation with Chlamydia Since T cells in OT1 mice are engineered to recognize only the OVA_457-462 epitope, the above observations have demonstrated a chlamydial antigen-independent immune mechanism for regulating chlamydial pathogenicity. Further characterization of this mechanism may provide information for developing strategies to reduce infertility-causing pathology induced by infections.

SUBMITTER: Xie L

PROVIDER: S-EPMC7504968 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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Suppression of Chlamydial Pathogenicity by Nonspecific CD8⁺ T Lymphocytes.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Suppression of Chlamydial Pathogenicity by Nonspecific CD8+ T Lymphocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Suppression of Chlamydial Pathogenicity by Nonspecific CD8⁺ T Lymphocytes.