Sepsis-Induced T Cell Immunoparalysis: The Ins and Outs of Impaired T Cell Immunity

Jensen, Isaac J.; Sjaastad, Frances V.; Griffith, Thomas S.; Badovinac, Vladimir P.

doi:10.4049/jimmunol.1701618

Cited by 142 publications

(46 citation statements)

References 145 publications

(155 reference statements)

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“…1,3,12,13 A human acute monocytic leukemic cell line (THP-1 cell) is differentiated by PMA into macrophages and a lymphoblast cell line (Jurkat cell) was used as a model to study the crucial role of T lymphocytes. 4,5 Therefore, this study was conducted using THP-1 cells and Jurkat cells. This study is meaningful not only to confirm the action of PTX in macrophages and T lymphocytes but also to investigate the effects of PTX on T lymphocytes with hyper-inflammatory macrophages using co-culture.…”

Section: Discussionmentioning

confidence: 99%

“…Toll-like receptor 4 is expressed on the surface of monocytes and macrophages by LPS and activates NF-κB and ERK/MAPK pathways to secrete cytokines like TNFα, IL-1β, IL-6, IL-10, etc. [3][4][5]14 Migration inhibitory factor is secreted into the bloodstream during the process in which TLR recognizes bacteria or immune complexes to produce NF-κB, which in turn activates CD44/CD74 on the cell surface, thereby upregulating the expression of TLR on the cell surface and activation of NF-kB in the cell. 7,8 Also, MIF inhibits p53-mediated apoptosis, promotes cell proliferation, and overrides the anti-inflammatory effects of glucocorticoids.…”

Section: Discussionmentioning

confidence: 99%

“…However, severe hyper-inflammatory conditions, caused by various triggers, can lead to many complications including, systemic inflammatory response syndrome, immune-paralysis, and compensatory anti-inflammatory response syndrome. 4,5 In the case of various injuries, monocytes and neutrophils react in the early stages of the injury. Monocytes in the blood vessels migrate to the damaged tissue and differentiate into local macrophages.…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of pentoxifylline on T-cell viability under inflammatory conditions

et al. 2022

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Introduction: Pentoxifylline (PTX) reduces the levels of pro-inflammatory cytokines; however, its effects on immune system is not well understood. The aim of this study was to investigate the effect of PTX on T cells under inflammatory conditions in co-culture with THP-1-derived macrophages. Methods: Toll-like receptor 4 (TLR4) and macrophage migration inhibitory factor (MIF) levels were measured after addition of PTX to lipopolysaccharide (LPS)-stimulated differentiated THP-1 cells. T cell viability and MIF levels were measured after PTX was added to prostaglandin E2 (PGE2)-stimulated Jurkat T-cell leukemia line. Co-culture was conducted to determine the effect of LPS-stimulated differentiated THP-1 cells that are affected by PTX on Jurkat cells. To prevent the direct effects of LPS and PTX on Jurkat cells, LPS and PTX were washed from THP-1 cells before co-culture. T cell viability and interleukin-2 (IL-2) levels were determined in Jurkat cells. Results: Increase in the MIF concentration and TLR4 expression level in differentiated THP-1 cells stimulated with LPS were reversed after PTX addition. However, PTX did not improve T cell viability in PGE2–stimulated Jurkat cells. Co-culturing Jurkat cell and LPS-stimulated differentiated THP-1 cells resulted in a decreased viability of T cells. The addition of PTX restored T cell viability to normal control levels and IL-2 expression level in Jurkat cells. Conclusion: LPS-stimulated THP-1-derived macrophages reduced the T cell viability under inflammation. However, PTX restored T cells viability and IL-2 back to normal levels. Therefore, the immunomodulatory action of PTX may be mediated by macrophage-T cell interactions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protective effects of pentoxifylline on T-cell viability under inflammatory conditions

et al. 2022

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“…Sepsis significantly reduces the number of lymphocytes ( 127 – 130 ), including CD8 T cells, via apoptosis ( 131 – 133 ). While naive (T N ) CD8 T cells are more susceptible to radiation-induced apoptosis and are lost to a greater extent than T CIRCM cells ( 134 ), both T N and T CIRCM cells display similar susceptibility to the sepsis-induced numerical decline ( 135 – 137 ). Additionally, further investigation into the subset composition of T CIRCM cells before and after sepsis reveals the numerical decline of T CM is equal to that of CD62L - T EM cells.…”

Section: Short- and Long-term Impact Of Sepsis On The Composition Of ...mentioning

confidence: 99%

Sepsis-induced changes in differentiation, maintenance, and function of memory CD8 T cell subsets

2023

Self Cite

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Formation of long-lasting memory lymphocytes is one of the foundational characteristics of adaptive immunity and the basis of many vaccination strategies. Following the rapid expansion and contraction of effector CD8 T cells, the surviving antigen (Ag)-specific cells give rise to the memory CD8 T cells that persist for a long time and are phenotypically and functionally distinct from their naïve counterparts. Significant heterogeneity exists within the memory CD8 T cell pool, as different subsets display distinct tissue localization preferences, cytotoxic ability, and proliferative capacity, but all memory CD8 T cells are equipped to mount an enhanced immune response upon Ag re-encounter. Memory CD8 T cells demonstrate numerical stability under homeostatic conditions, but sepsis causes a significant decline in the number of memory CD8 T cells and diminishes their Ag-dependent and -independent functions. Sepsis also rewires the transcriptional profile of memory CD8 T cells, which profoundly impacts memory CD8 T cell differentiation and, ultimately, the protective capacity of memory CD8 T cells upon subsequent stimulation. This review delves into different aspects of memory CD8 T cell subsets as well as the immediate and long-term impact of sepsis on memory CD8 T cell biology.

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“…4 However, specific guidelines are still lacking in the judgment of the therapeutic effect and prognosis of the disease, and how to judge the severity and prognosis of the disease is extremely important in clinical work. Studies have concluded that 5 that the level of lymphocyte subsets in peripheral blood of patients with sepsis is closely related to their prognosis. PCT has high clinical application value in sepsis, and can be used as a reliable indicator for the diagnosis of sepsis.…”

Section: Introductionmentioning

confidence: 99%

Study on the Correlation and Clinical Significance of T lymphocyte Subsets, IL-6 and PCT in the Severity of Patients with Sepsis

Yan²,

Li³

et al. 2022

Pak J Med Sci

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Objective: To evaluate the correlation and clinical significance of T lymphocyte subsets, IL-6 and PCT in the severity of patients with sepsis. Methods: One-hundred and twenty patients with sepsis admitted to Baoding No.1 Central Hospital from March 05, 2021 to March 05, 2022 were selected and divided into three groups according to the severity of the disease: the sepsis group, the severe sepsis group and the septic shock group, with 40 cases in each group. The venous blood of all patients was drawn with a sterile vacuum blood collection tube after admission to detect the levels of T lymphocyte subsets CD3+, CD4+, CD8+, CD4+/CD8+, and the venous blood was collected to detect the levels of interleukin-6 (IL-6) and procalcitonin (PCT). The three groups of patients were compared to analyze whether there were differences, and whether there was a correlation between the level of each indicator and the prognosis of patients after treatment. Results: The levels of CD3+, CD4+ and CD4+/CD8+ in the three groups decreased with the aggravation of the disease, with a significant difference (p=0.00). The levels of IL-6 and PCT increased with the aggravation of the disease among the three groups, with statistically significant differences (IL-6, p=0.00; PCT, p=0.01). The better the patients recovered after treatment, the higher the levels of CD4+ and CD4+/CD8+, and the two were positively correlated; While the lower the levels of IL-6 and PCT, the two were negatively correlated. Conclusion: Peripheral blood T lymphocyte subsets and serum IL-6, PCT are abnormally expressed in patients with sepsis, and have a close bearing on the severity of the disease, which has a certain predictive value for patients after recovery. In view of this, the above indicators are of high clinical significance. doi: https://doi.org/10.12669/pjms.39.1.5711 How to cite this: Li Q, Yan W, Liu S, Li H. Study on the Correlation and Clinical Significance of T lymphocyte Subsets, IL-6 and PCT in the Severity of Patients with Sepsis. Pak J Med Sci. 2023;39(1):---------. doi: https://doi.org/10.12669/pjms.39.1.5711 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Sepsis-Induced T Cell Immunoparalysis: The Ins and Outs of Impaired T Cell Immunity

Cited by 142 publications

References 145 publications

Protective effects of pentoxifylline on T-cell viability under inflammatory conditions

Protective effects of pentoxifylline on T-cell viability under inflammatory conditions

Sepsis-induced changes in differentiation, maintenance, and function of memory CD8 T cell subsets

Study on the Correlation and Clinical Significance of T lymphocyte Subsets, IL-6 and PCT in the Severity of Patients with Sepsis

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