Human CD4+CD25+ T cells expressing a chimeric antigen receptor against aberrant superoxide dismutase 1 trigger antigen-specific immunomodulation

Graber, David J.; Cook, W. James; Sentman, Marie-Louise; Murad-Mabaera, Joana M.; Sentman, Charles L.

doi:10.1016/j.jcyt.2023.11.007

Cited by 4 publications

(1 citation statement)

References 49 publications

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“…The molecular profiles, signaling pathways, antigen specificities, and infiltration routes of such neurotoxic T cell subsets can all be valuable diagnostic and therapeutic targets. In addition, further understanding of the infiltration process and synapse formation of T cells with brain APCs can be harnessed to develop novel immunoregulatory approaches such as the use of antigen-specific Tregs or chimeric antigen receptor (CAR) T cells that target specific antigens within the CNS [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

CD4 T-cell aging exacerbates neuroinflammation in a late-onset mouse model of amyotrophic lateral sclerosis

Zaccai,

Nemirovsky,

Lerner

et al. 2024

J Neuroinflammation

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Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons in the brain and spinal cord. Accumulating evidence suggests that ALS is not solely a neuronal cell- or brain tissue-autonomous disease and that neuroinflammation plays a key role in disease progression. Furthermore, whereas both CD4 and CD8 T cells were observed in spinal cords of ALS patients and in mouse models of the disease, their role in the neuroinflammatory process, especially considering their functional changes with age, is not fully explored. In this study, we revealed the structure of the CD4 T-cell compartment during disease progression of early-onset SOD1G93A and late-onset SOD1G37R mouse models of ALS. We show age-related changes in the CD4 T-cell subset organization between these mutant SOD1 mouse models towards increased frequency of effector T cells in spleens of SOD1G37R mice and robust infiltration of CD4 T cells expressing activation markers and the checkpoint molecule PD1 into the spinal cord. The frequency of infiltrating CD4 T cells correlated with the frequency of infiltrating CD8 T cells which displayed a more exhausted phenotype. Moreover, RNA-Seq and immunohistochemistry analyses of spinal cords from SOD1G37R mice with early clinical symptoms demonstrated immunological trajectories reminiscent of a neurotoxic inflammatory response which involved proinflammatory T cells and antigen presentation related pathways. Overall, our findings suggest that age-related changes of the CD4 T cell landscape is indicative of a chronic inflammatory response, which aggravates the disease process and can be therapeutically targeted.

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Section: Discussionmentioning

confidence: 99%

CD4 T-cell aging exacerbates neuroinflammation in a late-onset mouse model of amyotrophic lateral sclerosis

Zaccai,

Nemirovsky,

Lerner

et al. 2024

J Neuroinflammation

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Immune mechanisms and shared immune targets in neurodegenerative diseases

Weiner

2024

Nat Rev Neurol

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CD4+ T-Cell Senescence in Neurodegenerative Disease: Pathogenesis and Potential Therapeutic Targets

Gao,

Lu,

Liang

et al. 2024

Cells

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With the increasing proportion of the aging population, neurodegenerative diseases have become one of the major health issues in society. Neurodegenerative diseases (NDs), including multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neurodegeneration associated with aging, leading to a gradual decline in cognitive, emotional, and motor functions in patients. The process of aging is a normal physiological process in human life and is accompanied by the aging of the immune system, which is known as immunosenescence. T-cells are an important part of the immune system, and their senescence is the main feature of immunosenescence. The appearance of senescent T-cells has been shown to potentially lead to chronic inflammation and tissue damage, with some studies indicating a direct link between T-cell senescence, inflammation, and neuronal damage. The role of these subsets with different functions in NDs is still under debate. A growing body of evidence suggests that in people with a ND, there is a prevalence of CD4+ T-cell subsets exhibiting characteristics that are linked to senescence. This underscores the significance of CD4+ T-cells in NDs. In this review, we summarize the classification and function of CD4+ T-cell subpopulations, the characteristics of CD4+ T-cell senescence, the potential roles of these cells in animal models and human studies of NDs, and therapeutic strategies targeting CD4+ T-cell senescence.

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Human CD4+CD25+ T cells expressing a chimeric antigen receptor against aberrant superoxide dismutase 1 trigger antigen-specific immunomodulation

Cited by 4 publications

References 49 publications

CD4 T-cell aging exacerbates neuroinflammation in a late-onset mouse model of amyotrophic lateral sclerosis

CD4 T-cell aging exacerbates neuroinflammation in a late-onset mouse model of amyotrophic lateral sclerosis

Immune mechanisms and shared immune targets in neurodegenerative diseases

CD4+ T-Cell Senescence in Neurodegenerative Disease: Pathogenesis and Potential Therapeutic Targets

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