ArticleTranslational psychiatry2013
CD4⁺ but not CD8⁺ T cells revert the impaired emotional behavior of immunocompromised RAG-1-deficient mice.
Article in Translational psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 111 citations in OpenAlex.
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- Spatial Cell Atlas of Lateral Septum Reveals Changes Underlying Anxiety and Fear Learning Deficits in Mice with Abnormal Immunity.International journal of biological sciences · 2025Article
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- Integrated Single-Cell RNA-seq and ATAC-seq Reveals Heterogeneous Differentiation of CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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- Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review.International journal of molecular sciences · 2024Review
- Maternal immunoglobulins are distributed in the offspring's brain to support the maintenance of cortical interneurons in the postnatal period.Inflammation and regeneration · 2024Article
- Will cellular immunotherapies end neurodegenerative diseases?Trends in immunology · 2024Article
- B cells and the stressed brain: emerging evidence of neuroimmune interactions in the context of psychosocial stress and major depression.Frontiers in cellular neuroscience · 2024Review
- Clinically approved immunomodulators ameliorate behavioral changes in a mouse model of hereditary spastic paraplegia type 11.Frontiers in neuroscience · 2024Article
- Astrocytic engagement of the corticostriatal synaptic cleft is disrupted in a mouse model of Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment.Nature communications · 2023Article
- T cells: an emerging cast of roles in bipolar disorder.Translational psychiatry · 2023Review
- Meningeal T cells function in the central nervous system homeostasis and neurodegenerative diseases.Frontiers in cellular neuroscience · 2023Review
- Basic principles of neuroimmunology.Seminars in immunopathology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An imbalanced immune system has long been known to influence a variety of mood disorders including anxiety, obsessive-compulsive disorders and depression. In this study, we sought to model the impact of an immunocompromised state on these emotional behaviors using RAG-1⁻/⁻ mice, which lack T and B cells. We also investigated the relative contribution of CD4⁺ or CD8⁺ T cells to these manifestations using RAG-1⁻/⁻/OT-II and RAG-1⁻/⁻/OT-I transgenic mice, respectively. Our results show that RAG-1⁻/⁻ mice present a significant increase in digging and marble-burying activities compared with wild-type mice. Surprisingly, these anxiety-like behaviors were significantly reverted in RAG-1⁻/⁻/OT-II but not RAG-1⁻/⁻/OT-I transgenic mice. Immunodepletion experiments with anti-CD4 or anti-CD8 in C57/BL6 mice or repopulation studies in RAG-1⁻/⁻ mice did not reproduce these findings. Microarray analysis of the brain of RAG-1⁻/⁻ and RAG-1⁻/⁻/OT-II mice revealed a significantly different gene fingerprint, with the latter being more similar to wild-type mice than the former. Further analysis revealed nine main signaling pathways as being significantly modulated in RAG-1⁻/⁻ compared with wild-type mice. Taken together, these results suggest that life-long rather than transient immunodeficient conditions influence the emotional behaviors in mice. Most interestingly, these effects seem to correlate with a specific absence of CD4⁺ rather than CD8⁺ T cells. Validation of these findings in man might provide new clues on the mechanism by which early life immune modulation might impact mood response in adults and provide a further link between immune and emotional well-being.
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