The Road to Memory: An Early Rest for the Long Journey

摘要

Central memory T lymphocytes were reported to develop after acute but not chronic infection, which prompted this feasibility study on generating long-term CD8 T cells ex vivo, by applying a culture condition that simulates an acute infection. During 35 d of culture, naive T cells (CD45RA+, CD127+, CCR7+, CD62L+, CXCR3+) first developed into effector T cells (CD45RA+/?, CD127+/?, CCR7+/?, CD62L+, CXCR3+), followed by three intermediate stages: intermediate T cells 1 (CD45RO+, CD127+/?, CCR7+, CD62L+, CXCR3+), intermediate T cells 2 (CD45RO+, CD127?, CCR7?, CD62L+, CXCR3+), and intermediate T cells 3 (CD45RO+/?, CD127+, CCR7+, CD62L?, CXCR3+) before reverting to stable CD45RA+ central memory T cells (CD45RA+, CD127+, CCR7+, CD62L+, CXCR3+). If both anti-CD3 and the inflammatory milieu persisted beyond day 10, intermediate T cells 2 gradually developed into effector memory T cells (CD45RO+, CD127?, CCR7?, CD62L?, CXCR3+). Furthermore, intermediate T cells 2 or effector memory T cells, when cultured in persistent inflammatory cytokines devoid of anti-CD3, were converted to central memory T cells (CD45RO+, CCR7+, CD62L+). Overall, these results support ex vivo memory-like T lymphocyte production and favor a developmental pathway including both divergent and linear relationships.