Loss of T cells influences sex differences in behavior and brain structure

Rilett, Kelly C.; Friedel, Miriam; Ellegood, Jacob; MacKenzie, Robyn N.; Lerch, Jason P.; Foster, Jane A.

doi:10.1016/j.bbi.2015.02.016

Cited by 36 publications

(47 citation statements)

References 92 publications

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“…Nevertheless, the fact that CD4 + T cells were unable to modify the behavioral phenotype in Rag2 −/− mice presents a number of possible scenarios. First, T cells may affect the development of the CNS leading to stable phenotypes, as was demonstrated in T cell receptor beta-delta chain knock-out mice (TCRβ-/∂-) (Rilett et al, 2015). In this study the authors showed a role for functional T cells during brain development, including changes in the volume of specific brain structures with a loss of sexual dimorphism, two stable changes in the CNS.…”

Section: Discussionmentioning

confidence: 99%

“…Secondly, since Rag2 −/− mice are also deficient in B cell function, startle reactivity may be dependent on these cells. However, many studies have shown that behavioral effects of lymphocytes are independent of B cell function (Radjavi et al, 2014; Rilett et al, 2015). Finally, the lack of effect of CD4 + T cells may be related to a floor effect in which startle reactivity cannot be modified below the threshold displayed by non-reconstituted Rag2 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

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CD4⁺T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes inRag2^−/−mice

Clark

Soroka

Song

et al. 2016

Stress

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Accumulating evidence supports a role for T cells in behavioral stress responsiveness. Our laboratory previously reported that lymphocyte deficient Rag2−/− mice on a BALB/c background display resilience to maladaptive stress responses when compared with immune competent mice in the predator odor exposure (POE) paradigm while exhibiting similar behavior in a cued fear-conditioning (FC) paradigm. In the present study Rag2−/− mice on a C57BL/6 background were assessed in the same behavioral paradigms, as well additional tests of anxiety and depressive-like behavior. Furthermore, the effects of naïve CD4+ T cells were evaluated by adoptive transfer of functional cells from non-stressed, wild-type donors to Rag2−/− mice. Consistent with our prior results, Rag2−/− mice displayed an attenuated startle response after POE. Nevertheless, reconstitution of Rag2−/− mice with CD4+ T cells did not modify startle reactivity. Additionally, in contrast with our previous findings, Rag2−/− mice showed attenuated fear responses in the FC paradigm compared to wild type mice and reconstitution with CD4+ T cells promoted fear learning and memory. Notably, reconstitution with CD4+ T cells had anxiolytic and anti-depressant like effects in Rag2−/− mice that had not been previously stressed, but had no effect after POE. Taken together, our results support a role for CD4+ T cells in emotionality, but also indicate that they may promote fear responses by enhancing learning and memory processes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CD4⁺T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes inRag2^−/−mice

Clark

Soroka

Song

et al. 2016

Stress

View full text Add to dashboard Cite

show abstract

“…T cells from the thymus reside in the meninges, and recent studies have found that T cell-deficient mice have impairments in adult behaviours, including spatial learning and social behaviour 57,58 . A separate study examined the role of T cells on brain development 59 . In adulthood, the bed nucleus of the stria terminalis (BNST), a brain region that is contiguous with the POA and is both highly sexually dimorphic and sexually differentiated by steroid hormones during development 60 , was masculinized, that is, increased in size, in female mice congenitally lacking T cells.…”

Section: Mechanisms Of Sexual Differentiationmentioning

confidence: 99%

Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain

2017

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The study of sex differences in the brain is a topic of neuroscientific study that has broad reaching implications for culture, society and biomedical science. Recent research in rodent models has led to dramatic shifts in our views of the mechanisms underlying the sexual differentiation of the brain. These include the surprising discoveries of a role for immune cells and inflammatory mediators in brain masculinization and a role for epigenetic suppression in brain feminization. How and to what degree these findings will translate to human brain development will be questions of central importance in future research in this field.

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“…In another study, SCID mice showed social interaction deficits but not increased anxiety compared to their C57BL/6 wildtype counterparts (Filiano et al, 2016). TCRβ −/− δ −/− mice had minor abnormalities in anxiety behavior that were sex-dependent (Rilett et al, 2015). Some of the conflicting data presented here may still be resolved by careful examination of a number of factors, such as strain and age of animals, nature of the task, and microbiota differences that might be related to standards of cleanliness in the facilities housing these immune-compromised animals.…”

Section: Adaptive Immunity In Affective Disordersmentioning

confidence: 99%

Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

Herkenham

Kigar

2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Clinical and basic studies of functional interactions between adaptive immunity, affective states, and brain function are reviewed, and the neural, humoral, and cellular routes of bidirectional communication between the brain and the adaptive immune system are evaluated. In clinical studies of depressed populations, lymphocytes—the principal cells of the adaptive immune system—exhibit altered T cell subtype ratios and CD4+ helper T cell polarization profiles. In basic studies using psychological stress to model depression, T cell profiles are altered as well, consistent with stress effects conveyed by the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Lymphocytes in turn have effects on behavior and CNS structure and function. CD4+ T cells in particular appear to modify affective behavior and rates of hippocampal dentate gyrus neurogenesis. These observations force the question of how such actions are carried out. CNS effects may occur via cellular and molecular mechanisms whereby effector memory T cells and the cytokine profiles they produce in the blood interact with the blood-brain barrier in ways that remain to be clarified. Understanding the mechanisms by which T cells polarize and interact with the brain to alter mood states is key to advances in the field, and may permit development of therapies that target cells in the periphery, thus bypassing problems associated with bioavailability of drugs within the brain.

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Loss of T cells influences sex differences in behavior and brain structure

Cited by 36 publications

References 92 publications

CD4⁺T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes inRag2^−/−mice

CD4⁺T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes inRag2^−/−mice

Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain

Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

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Loss of T cells influences sex differences in behavior and brain structure

Cited by 36 publications

References 92 publications

CD4+T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes inRag2−/−mice

CD4+T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes inRag2−/−mice

Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain

Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

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Product

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CD4⁺T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes inRag2^−/−mice

CD4⁺T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes inRag2^−/−mice