Emerging data suggest that sepsis survivors frequently experience long-term mental impairment after discharge. This is assumed to be caused by sepsis-associated encephalopathy (SAE) ; however, the relationship between the onset of long-term mental impairments and SAE is still unclear. In addition, several studies have revealed that the development of mental impairment results in neuroinflammation, which is induced by aberrant activated immune cells, including glial cells and T cells. However, it is still unclear how these immune cells contribute to the pathogenesis and attenuation of SAE. In this study, we performed animal behavioral tests and found that anxiety-like behavior was exacerbated in mice with sepsis. Furthermore, these mice had elevated levels of pro-inflammatory cytokines such as interleukin (IL)-1β in the brain, depending on the severity of sepsis. Interestingly, sepsis induced an increase in microglia and a decrease in astrocytes in mice during the acute/subacute phase ; T cell numbers also increased in the brains of mice with sepsis. To investigate how brain-accumulated T cells influence the development of SAE and mental impairments, we treated mice with sepsis with FTY720 to inhibit recruitment. This immunomodulator delayed the recovery of anxiety-like behavior, and the number of astrocytes in the brain remained reduced during the chronic phase of sepsis in mice. Additionally, the expression of Il1b in the brains of FTY720-treated mice with sepsis had increased during the chronic phase. Our findings suggest that infiltrated T cells contribute to the attenuation of SAE and alleviate SAE-induced mental disorders by alleviating neuroinflammation in the chronic phase of sepsis.
