Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis
| Autor: | Jennifer M. Robertson, Craig M. Coopersmith, Mandy L. Ford, Ching-Wen Chen, Jianfeng Xie, Wenxiao Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male 0301 basic medicine Physiology medicine.medical_treatment lcsh:Medicine Pathology and Laboratory Medicine Memory T cells Mice White Blood Cells Spectrum Analysis Techniques Animal Cells Neoplasms Immune Physiology Prevalence Medicine and Health Sciences lcsh:Science Staining Innate Immune System education.field_of_study Multidisciplinary medicine.diagnostic_test T Cells Cell Staining Animal Models Flow Cytometry 3. Good health Cytokine medicine.anatomical_structure Experimental Organism Systems Spectrophotometry Cytokines Female Tumor necrosis factor alpha Cytophotometry Cellular Types Research Article Death Rates Immune Cells T cell Immunology Population Mouse Models Biology Research and Analysis Methods Malignancy Flow cytometry Sepsis 03 medical and health sciences Signs and Symptoms Model Organisms Population Metrics Diagnostic Medicine medicine Animals education Blood Cells Population Biology lcsh:R Biology and Life Sciences Cancer Cell Biology Molecular Development medicine.disease 030104 developmental biology Specimen Preparation and Treatment Case-Control Studies Immune System lcsh:Q Developmental Biology |
| Zdroj: | PLoS ONE, Vol 13, Iss 1, p e0191065 (2018) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events) were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naïve CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre-existing malignancy following sepsis. |
| Databáze: | OpenAIRE |
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