Resident memory CD4(+) T lymphocytes mobilize from bone marrow to contribute to a systemic secondary immune reaction

Resident memory T lymphocytes (T-RM) of epithelial tissues and the Bm protect their host tissue. To what extent these cells are mobilized and contribute to systemic immune reactions is less clear. Here, we show that in secondary immune reactions to the measles-mumps-rubella (MMR) vaccine, CD4(+) T-RM are mobilized into the blood within 16 to 48 h after immunization in humans. This mobilization of T-RM is cognate: T-RM recognizing other antigens are not mobilized, unless they cross-react with the vaccine. We also demonstrate through methylome analyses that T-RM are mobilized from the Bm. These mobilized cells make significant contribution to the systemic immune reaction, as evidenced by their T-cell receptor V beta clonotypes represented among the newly generated circulating memory T-cells, 14 days after vaccination. Thus, T-RM of the Bm confer not only local, but also systemic immune memory.