CXCR4 is critical for CD8+ memory T cell homeostatic self-renewal but not rechallenge self-renewal

摘要

Central memory (CM) CD8⁺ T cells “remember” prior encounters because they maintain themselves through cell division in the absence of ongoing challenge (homeostatic self-renewal) as well as reproduce the central memory fate while manufacturing effector cells during secondary antigen encounters (rechallenge self-renewal). We tested the consequence of conditional deletion of the bone marrow (BM) homing receptor CXCR4 on antiviral T cell responses. CXCR4-deficient CD8⁺ T cells have impaired memory cell maintenance due to defective homeostatic proliferation. Upon rechallenge, however, CXCR4-deficient T cells can re-expand and renew the central memory pool while producing secondary effector cells. The critical BM-derived signals essential for CD8⁺ T cell homeostatic self-renewal appear to be dispensable to yield self-renewing, functionally asymmetric cell fates during rechallenge.