Inflammatory CD4/CD8 double-positive human T cells arise from reactive CD8 T cells and are sufficient to mediate GVHD pathology

Hess, Nicholas J; Turicek, David P; Riendeau, Jeremiah; McIlwain, Sean J.; Guzman, Emmanuel Contreras; Nadiminti, Kalyan; Hudson, Amy W.; Callander, Natalie S.; Skala, Melissa C.; Gumperz, Jenny E.; Hematti, Peiman; Capitini, Christian M.

doi:10.1126/sciadv.adf0567

Cited by 11 publications

(5 citation statements)

References 65 publications

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“…In addition, the expansion of DP T cells in RA is associated with joint damage and frequent escalation of therapy [70]. Another example of DP T cell presence in inflammation is the development of graft versus host disease (GVHD), which has been recently associated with the appearance of a DP T cell population that was originally not present in the graft [72].…”

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confidence: 99%

Legend or Truth: Mature CD4+CD8+ Double-Positive T Cells in the Periphery in Health and Disease

Hagen,

Pangrazzi,

Rocamora-Reverte

et al. 2023

Biomedicines

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The expression of CD4 and CD8 co-receptors defines two distinct T cell populations with specialized functions. While CD4+ T cells support and modulate immune responses through different T-helper (Th) and regulatory subtypes, CD8+ T cells eliminate cells that might threaten the organism, for example, virus-infected or tumor cells. However, a paradoxical population of CD4+CD8+ double-positive (DP) T cells challenging this paradigm has been found in the peripheral blood. This subset has been observed in healthy as well as pathological conditions, suggesting unique and well-defined functions. Furthermore, DP T cells express activation markers and exhibit memory-like features, displaying an effector memory (EM) and central memory (CM) phenotype. A subset expressing high CD4 (CD4bright+) and intermediate CD8 (CD8dim+) levels and a population of CD8bright+CD4dim+ T cells have been identified within DP T cells, suggesting that this small subpopulation may be heterogeneous. This review summarizes the current literature on DP T cells in humans in health and diseases. In addition, we point out that strategies to better characterize this minor T cell subset’s role in regulating immune responses are necessary.

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confidence: 99%

Legend or Truth: Mature CD4+CD8+ Double-Positive T Cells in the Periphery in Health and Disease

Hagen,

Pangrazzi,

Rocamora-Reverte

et al. 2023

Biomedicines

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“…Chicken-specific studies suggest that these cells are of a CD4 + T cell origin ( 54 ) and that their presence in the periphery increases with age (Erf et al., 1998) ( 55 ). Recent data from mammals suggest that CD4 + CD8α + are antigen-experienced and possibly of CD8-origin ( 56 , 57 ).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous immunological activities in the target tissue of vitiligo-prone Smyth and vitiligo-susceptible Brown lines of chicken

Falcon,

Byrne,

Sales

et al. 2024

Front. Immunol.

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IntroductionVitiligo is an acquired de-pigmentation disorder characterized by the post-natal loss of epidermal melanocytes (pigment-producing cells) resulting in the appearance of white patches in the skin. The Smyth chicken is the only model for vitiligo that shares all the characteristics of the human condition including: spontaneous post-natal loss of epidermal melanocytes, interactions between genetic, environmental and immunological factors, and associations with other autoimmune diseases. In addition, an avian model for vitiligo has the added benefit of an easily accessible target tissue (a growing feather) that allows for the repeated sampling of an individual and thus the continuous monitoring of local immune responses over time.MethodsUsing a combination of flow cytometry and gene expression analyses, we sought to gain a comprehensive understanding of the initiating events leading to expression of vitiligo in growing feathers by monitoring the infiltration of leukocytes and concurrent immunological activities in the target tissue beginning prior to visual onset and continuing throughout disease development.ResultsHere, we document a sequence of immunologically significant events, including characteristic rises in infiltrating B and αβ T cells as well as evidence of active leukocyte recruitment and cell-mediated immune activities (CCL19, IFNG, GZMA) leading up to visual vitiligo onset. Examination of growing feathers from vitiligo-susceptible Brown line chickens revealed anti-inflammatory immune activities which may be responsible for preventing vitiligo (IL10, CTLA4, FOXP3). Furthermore, we detected positive correlations between infiltrating T cells and changes in their T cell receptor diversity supporting a T cell-specific immune response.ConclusionCollectively, these results further support the notion of cell-mediated immune destruction of epidermal melanocytes in the pulp of growing feathers and open new avenues of study in the vitiligo-prone Smyth and vitiligo-susceptible Brown line chickens.

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“…However, its negative effects were found in some studies. One study found that reveals human DPTs as a T cell population directly involved with graft-versus-host disease (GVHD) pathology ( 68 ). Expansion of DPT cells is associated with joint damage and frequent escalation of therapy, possibly suggesting a contribution to more severe rheumatoid arthritis ( 69 ).…”

Section: Discussionmentioning

confidence: 99%

Regulatory effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin on inflammation and immune function in percutaneous nephrolithotomy patients with upper urinary tract calculi complicated with infection

2023

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ObjectiveTo study the effect of an injection of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on inflammation and immune function in patients with upper urinary tract calculi complicated by infection who have undergone percutaneous nephrolithotomy.MethodsWe retrospectively recorded the clinical data of patients with upper urinary tract calculi complicated by infection who have undergone Percutaneous nephrolithotomy(PCNL) in the Department of Urology, 2nd Affiliation Hospital of Kunming Medical University, from March to December 2021. Clinical data include general condition, laboratory index, CT, postoperative body temperature, heart rate, respiration, SIRS, sepsis, etc. Patients were divided into treated and control groups according to whether they had received a preoperative PA-MSHA injection. The two groups were compared for indices of inflammation and complications of infection after PCNL. Pre- and post-operative lymphocyte subsets and immunoglobulin changes were compared.Results115 patients were included in the study, including 43 in the treatment group and 72 in the control group. After Propensity Score Matching, 90 patients were divided into treatment (n=35) and control (n=55) groups. The postoperative inflammation index was higher in the treatment group than in the control group (P<0.05). The incidence of postoperative SIRS was higher in the treatment group than control (P<0.05). There were no cases of sepsis in either group. The double-positive T cells lymphocyte subsets were higher in the treatment group than in the control group ((P<0.05). Pre- and post-operative changes in immune function: total T lymphocyte count reduced, NK and NKT cell count increased in the control group, double-positive T cell count increased in the treatment group, IgG, IgA, IgM, complement C3 and C4 count reduced in both groups post-operatively.ConclusionThis study found that patients with upper urinary tract calculi and infection treated with antibiotic-based PA-MSHA before percutaneous nephrolithotomy had an increased inflammatory response after surgery, which may play a role in the prevention and treatment of sepsis. The percentage of double-positive T cells in the peripheral blood was increased after PA-MSHA treatment, which may have an immunomodulatory and protective effect in PCNL patients with stones complicated by infection.

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Inflammatory CD4/CD8 double-positive human T cells arise from reactive CD8 T cells and are sufficient to mediate GVHD pathology

Cited by 11 publications

References 65 publications

Legend or Truth: Mature CD4+CD8+ Double-Positive T Cells in the Periphery in Health and Disease

Legend or Truth: Mature CD4+CD8+ Double-Positive T Cells in the Periphery in Health and Disease

Spontaneous immunological activities in the target tissue of vitiligo-prone Smyth and vitiligo-susceptible Brown lines of chicken

Regulatory effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin on inflammation and immune function in percutaneous nephrolithotomy patients with upper urinary tract calculi complicated with infection

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