title: CD4⁺ but not CD8⁺ T cells revert the impaired emotional behavior of immunocompromised RAG-1-deficient mice.
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.
authors.affiliation: Centre for Biochemical Pharmacology, The William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Rattazzi
authors.forename: G
authors.initials: G
authors.lastname: Piras
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: R
authors.initials: R
authors.lastname: Deacon
authors.forename: C M
authors.initials: CM
authors.lastname: Pariante
authors.forename: F
authors.initials: F
authors.lastname: D'Acquisto
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood; D004644:Emotions / Q000502:physiology*; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000502:physiology*; D016867:Immunocompromised Host / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D018398:Homeodomain Proteins; C064658:RAG-1 protein; D003345:Corticosterone