Removal of lymphocytes from the meningeal spaces in mice using fingolimod (sphingosine-1-phosphate receptor modulator) or anti-VLA4 also resulted in impaired learning outcomes ( 14). Pharmacological loss-of-function studies have also provided evidence of a role for T cells in neurodevelopment. Such findings are not restricted to murine models, as activated human T cells secrete bioactive BDNF that supports neuronal survival in vitro ( 13).

Rag1 −/− immunocompromised mice show increased depressive and anxiety-like behavior that is rescued by transplanting CD4 + T cells, but not CD8 + T cells ( 12). These deficits can be rescued in nude mice when T cells are repopulated by adoptive transfer from WT mice ( 11).

These mice had lower levels of brain-derived neurotrophic factor (BDNF), a higher number of cognitive deficits, and poor performance in the MWM. This impaired MWM performance was also evident in MHC II −/− mice that are deficient in CD4 + T cells but have CD8 + T cells, suggesting that CD4 or MHC II functionality is required for normal learning and memory performance ( 10).įurther evidence for roles of T cells in neurodevelopment comes from studies of mice deficient in mature T cells, in both nude (lacking T lymphocytes due to a disruption in the Foxn1 gene that causes deterioration of the thymus) and SCID mouse models. Rag2 −/− mice showed impaired learning/memory performance in the Morris water maze (MWM) task, but this impairment was not attributable to B cell deficiency as B cell-deficient mouse (μMT mice) performance was comparable to controls. Interestingly, mice with a T cell receptor against endogenous myelin basic protein (MBP) showed enhanced hippocampal neurogenesis and improved spatial learning in comparison to mice with a T cell receptor to non-self antigen ( 8). Neurogenesis impairment was found to be dependent on CD4 + lymphocytes, as transplantation of CD8 + lymphocytes into Rag2 −/− mice (lacking T and B cells) did not rescue the effect in the same manner ( 9). Hippocampal neurogenesis is dependent on the adaptive immune system, and is significantly impaired in severe combined immune deficiency (SCID) mice that lack T and B lymphocytes due to a Rag1/2 gene deletion ( 8). T cells in Brain Development and BEHAVIOR

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