TCR-α/β CD4− CD8− double negative T cells arise from CD8+ T cells

Rodríguez-Rodríguez, Noé; Flores-Mendoza, Giovanna; Apostolidis, Sokratis A.; Rosetti, Florencia; Tsokos, George C.; Crispín, José C.

doi:10.1002/jlb.1ab0120-548r

Cited by 22 publications

(12 citation statements)

References 31 publications

(35 reference statements)

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“…Previous research indicates that DN T cells are important members of both innate and adaptive immunity (32). However, our current understanding of DN T cells remains limited (33). Some postulate their potential regulatory functions, albeit with comparatively weak immunosuppressive abilities (34).…”

Section: Discussionmentioning

confidence: 99%

The Relationship Between Circulating Immune Cell Phenotypes and Sepsis: A Mendelian Randomization Study

Liu,

Zhou

et al. 2024

Shock

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Objective The role of immune cells in sepsis remains unclear, and there is some controversy. Here, we aim to systematically assess whether distinct immune cell phenotypes impact the susceptibility to sepsis. Methods In this study, we harnessed publicly available summary-level data from genome-wide association studies (GWAS). The selection of genetic variations strongly associated with 731 phenotypes of circulating immune cells served as instrumental variables (IVs). Using a two-sample Mendelian randomization (MR) analysis, we investigated the relationships between different immunophenotypes and the occurrence of sepsis, as well as the 28-day mortality. The MR study utilized the Inverse Variance Weighting (IVW) method as the main analytical approach. Additionally, we incorporated four other MR methods for supplementary causal inference, including Weighted Median (WME), MR-Egger regression, Simple Mode, and Weighted Mode. Furthermore, the robustness of the results was affirmed through multiple sensitivity analyses. Results The results of the IVW method indicated that a total of 36 immunophenotypes are associated with the risk of sepsis. we also identified 34 immunophenotypes with a causal association with the 28-day mortality. Interestingly, before multiple testing corrections, 11 immunophenotypes were determined to have consistent causal relationships with both the occurrence of sepsis and the 28-day mortality. Notably, after False Discovery Rate (FDR) correction, four immunophenotypes were found to be significantly correlated with susceptibility to sepsis: CD45RA− CD4+ %CD4 + (OR = 1.355, 95% CI = 1.139 ~ 1.611, P < 0.001, P FDR = 0.192), HLA DR on HLA DR+ NK(OR = 0.818, 95% CI = 0.726 ~ 0.922, P = 0.001, PFDR = 0.192), IgD+ CD24+ %B cell(OR = 0.626, 95% CI = 0.473 ~ 0.828, P = 0.001, PFDR = 0.192), TD DN (CD4 − CD8−) AC(OR = 0.655, 95% CI = 0.510 ~ 0.840, P < 0.001, PFDR = 0.192). Following FDR correction, only one immunophenotype was confirmed to be negatively correlated with the 28-day mortality: CD39 on CD39+ CD8br(OR = 0.820, 95% CI = 0.737 ~ 0.912, P < 0.001, PFDR = 0.184). Conclusion This study, for the first time, has uncovered indicative evidence of a causal relationship between circulating immune cell phenotypes and varying degrees of sepsis through genetic means. These findings underscore the significance of immune cells in the pathogenesis of sepsis.

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Section: Discussionmentioning

confidence: 99%

The Relationship Between Circulating Immune Cell Phenotypes and Sepsis: A Mendelian Randomization Study

Liu,

Zhou

et al. 2024

Shock

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“…DN T cells in the periphery are unable to proliferate and mainly converted from CD8 + T cells. They can re-express CD8 when lymphocytes are reduced ( 38 ). This is consistent with our observation in the UMAP plot that DN T cells were closer to CD8 + T cells.…”

Section: Discussionmentioning

confidence: 99%

Adenoid lymphocyte heterogeneity in pediatric adenoid hypertrophy and obstructive sleep apnea

et al. 2023

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IntroductionAdenoid hypertrophy is the main cause of obstructive sleep apnea in children. Previous studies have suggested that pathogenic infections and local immune system disorders in the adenoids are associated with adenoid hypertrophy. The abnormalities in the number and function of various lymphocyte subsets in the adenoids may play a role in this association. However, changes in the proportion of lymphocyte subsets in hypertrophic adenoids remain unclear.MethodsTo identify patterns of lymphocyte subsets in hypertrophic adenoids, we used multicolor flow cytometry to analyze the lymphocyte subset composition in two groups of children: the mild to moderate hypertrophy group (n = 10) and the severe hypertrophy group (n = 5).ResultsA significant increase in naïve lymphocytes and a decrease in effector lymphocytes were found in severe hypertrophic adenoids.DiscussionThis finding suggests that abnormal lymphocyte differentiation or migration may contribute to the development of adenoid hypertrophy. Our study provides valuable insights and clues into the immunological mechanism underlying adenoid hypertrophy.

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“…In previous work we have shown that exposure of CD8 + T cells to self-antigen induces an inactivation program that includes the downregulation of CD8 expression (25)(26)(27). Because we never observed CD8 downregulation during in vitro activation and CD8 loss was only observed in tissues locally expressing the cognate antigen (25), we hypothesized that repetitive encounter with antigen -as occurs in vivo during self-antigen encounter-may play a role in this process and that signaling through Fas or FasL may regulate CD8 loss.…”

Section: Discussionmentioning

confidence: 99%

“…A wealth of evidence indicates that DN T cells derive from CD8ab + T cells: (a) CD8 + and DN T cells share Vb usage and CDR3 sequences (19); (b) mice deficient in b2-microglobulin or MHC-I molecules have reduced numbers of DN T cells (20)(21)(22); (c) the Cd8a locus is hypomethylated in DN T cells, indicating previous transcriptional activity (23,24); (d) CD8 + T cells lose CD8 when they encounter cognate antigen presented as self (25,26); (e) DN T cells can upregulate CD8 when they undergo homeostatic proliferation under lymphopenia (27). Importantly, generation of DN T cells is not limited to situations in which Fas/ FasL function is compromised, as an increased abundance of DN T cells has been reported in a number of chronic inflammatory conditions that include systemic lupus erythematosus (15), primary Sjögren's syndrome (28), and psoriasis (29).…”

Section: Introductionmentioning

confidence: 99%

Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens

et al. 2021

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Activation of self-reactive CD8+ T cells induces a peripheral tolerance mechanism that involves loss of CD8 expression. Because genetic deficiency of Fas and Fasl causes the accumulation of double-negative (DN; CD3+ TCR-αβ+ CD4- CD8-) T cells that have been proposed to derive from CD8+ cells, we decided to explore the role of Fas and FasL in self-antigen-induced CD8 downregulation. To this end, we quantified Fas and FasL induction by different stimuli and analyzed the effects of Fas/FasL deficiency during a protective immune response and after exposure to self-antigens. Our data describes how Fas and FasL upregulation differs depending on the setting of CD8 T cell activation and demonstrates that Fas/FasL signaling maintains CD8 expression during repetitive antigen stimulation and following self-antigen encounter. Together, our results reveal an unexpected role of Fas/FasL signaling and offer a new insight into the role of these molecules in the regulation of immune tolerance.

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TCR-α/β CD4− CD8− double negative T cells arise from CD8+ T cells

Cited by 22 publications

References 31 publications

The Relationship Between Circulating Immune Cell Phenotypes and Sepsis: A Mendelian Randomization Study

The Relationship Between Circulating Immune Cell Phenotypes and Sepsis: A Mendelian Randomization Study

Adenoid lymphocyte heterogeneity in pediatric adenoid hypertrophy and obstructive sleep apnea

Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens

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