Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition

The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69+ CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI1M2FhN2U3N2E0NThjMjNlNGM2NjJjZmIxZGJmZDQ1OSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4NzEwMTc4fQ.Q26n-5GHnBOhiEvzbkWHRJx3DC8H9hgmSOhQdI9Un8RWWy8s_z-WOMmw1g3bDKWFugG0eEWi2UVDzbBfRLY2Cx5lrwRQfiTQmcwFEqnoW-EG68RIwAnc4vEH9WItwnvo6T9K6d3l1BwfA420naRy40VvGLfxo3IMyoTFG6o_F8e65qg5tBcmeuS7tspM1DvX9-xvx5qhEZwldBM3_TEHVLp7F0kbGW6KTEgE582WWK-wsc2CXJom7n8ocnII3kQnNJ8UnvQHrJKiN0JWT-W5ZyG4UsDGwRSFVbjAElPWrJp0sJBzMG1JA6f30MqD3NSQ92tMBnKWOY55BClVRVgmGA(mp4, (9.45 MB) Download video