Dataset Information

Cycling and activated CD8⁺ T lymphocytes and their association with disease severity in influenza patients.

ABSTRACT:

Background

T cell lymphopenia was a significant characteristic of severe influenza infection and it was associated with the functional changes of T cells. It is necessary to clarify the T cells characteristics of kinetic changes and their correlation with disease severity.

Methods

In a cohort of hospitalized influenza patients with varying degrees of severity, we characterized lymphocyte populations using flow cytometry.

Results

The numbers of cycling (Ki67⁺) T cells at the acute phase of severe influenza were higher, especially in the memory (CD45RO⁺) T cell subsets. T cells from hospitalized influenza patients also had significantly higher levels of the exhausted marker PD-1. Cycling status of T cells was associated with T cell activation during the acute phase of influenza infection. The recruitment of cycling and activated (CD38⁺HLA-DR⁺) CD8⁺ T cells subset is delayed in severe influenza patients.

Conclusions

The increased numbers of cycling memory (Ki67⁺CD45RO⁺) T cells subsets and delayed kinetics of activated (CD38⁺HLA-DR⁺) CD8⁺ T cells, could serve as possible biological markers for disease severity.

SUBMITTER: Liu S

PROVIDER: S-EPMC9441835 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Cycling and activated CD8<sup>+</sup> T lymphocytes and their association with disease severity in influenza patients.

Liu Shuai S Huang Zhisheng Z Fan Ruyue R Jia Ju J Deng Xiaoyan X Zou Xiaohui X Li Hui H Cao Bin B

BMC immunology 20220905 1

<h4>Background</h4>T cell lymphopenia was a significant characteristic of severe influenza infection and it was associated with the functional changes of T cells. It is necessary to clarify the T cells characteristics of kinetic changes and their correlation with disease severity.<h4>Methods</h4>In a cohort of hospitalized influenza patients with varying degrees of severity, we characterized lymphocyte populations using flow cytometry.<h4>Results</h4>The numbers of cycling (Ki67<sup>+</sup>) T c ...[more]

PMID: 36064355

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Project description:IntroductionInclusion body myositis (IBM) is a progressive inflammatory myopathy characterised by skeletal muscle infiltration and myofibre invasion by CD8+ T lymphocytes. In some cases, IBM has been reported to be associated with a systemic lymphoproliferative disorder of CD8+ T cells exhibiting a highly differentiated effector phenotype known as T cell Large Granular Lymphocytic Leukemia (T-LGLL).MethodsWe investigated the incidence of a CD8+ T-LGL lymphoproliferative disorder in 85 IBM patients and an aged-matched group of 56 Healthy Controls (HC). Further, we analysed the phenotypical characteristics of the expanded T-LGLs and investigated whether their occurrence was associated with any particular HLA alleles or clinical characteristics.ResultsBlood cell analysis by flow cytometry revealed expansion of T-LGLs in 34 of the 85 (40%) IBM patients. The T cell immunophenotype of T-LGLHIGH patients was characterised by increased expression of surface molecules including CD57 and KLRG1, and to a lesser extent of CD94 and CD56 predominantly in CD8+ T cells, although we also observed modest changes in CD4+ T cells and γδ T cells. Analysis of Ki67 in CD57+ KLRG1+ T cells revealed that only a small proportion of these cells was proliferating. Comparative analysis of CD8+ and CD4+ T cells isolated from matched blood and muscle samples donated by three patients indicated a consistent pattern of more pronounced alterations in muscles, although not significant due to small sample size. In the T-LGLHIGH patient group, we found increased frequencies of perforin-producing CD8+ and CD4+ T cells that were moderately correlated to combined CD57 and KLRG1 expression. Investigation of the HLA haplotypes of 75 IBM patients identified that carriage of the HLA-C*14:02:01 allele was significantly higher in T-LGLHIGH compared to T-LGLLOW individuals. Expansion of T-LGL was not significantly associated with seropositivity patient status for anti-cytosolic 5'-nucleotidase 1A autoantibodies. Clinically, the age at disease onset and disease duration were similar in the T-LGLHIGH and T-LGLLOW patient groups. However, metadata analysis of functional alterations indicated that patients with expanded T-LGL more frequently relied on mobility aids than T-LGLLOW patients indicating greater disease severity.ConclusionAltogether, these results suggest that T-LGL expansion occurring in IBM patients is correlated with exacerbated immune dysregulation and increased disease burden.

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

Cycling and activated CD8⁺ T lymphocytes and their association with disease severity in influenza patients.

Background

Methods

Results

Conclusions

Publications

Cycling and activated CD8<sup>+</sup> T lymphocytes and their association with disease severity in influenza patients.

Similar Datasets

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Dataset Information

Cycling and activated CD8+ T lymphocytes and their association with disease severity in influenza patients.

Background

Methods

Results

Conclusions

Publications

Cycling and activated CD8<sup>+</sup> T lymphocytes and their association with disease severity in influenza patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Cycling and activated CD8⁺ T lymphocytes and their association with disease severity in influenza patients.