A previously missed population of antigen-specific CD8 T cells divides in the blood after vaccination

Although clonal expansion is a hallmark of adaptive immunity, the location(s) where antigen-responding T cells enter cell cycle and complete it have been poorly explored. This lack of knowledge stems partially from the limited experimental approaches available. By using Ki67 plus DNA staining and a novel data analysis technique, we distinguished antigen-specific CD8 T cells in G0, in G1, and in S-G2-M phases after intramuscular vaccination of BALB/c mice with antigen-expressing viral vectors. We discovered an entire population of cycling cells that are usually missed. This \"extra\" population was present early after vaccination in lymph nodes, spleen and, surprisingly, also in the blood, which is not expected to be a site for mitosis of normal non-leukemic cells. These results have implications for previous and future immunological studies in animal models, and potentially in humans. They might also inspire hematologists to seek for other missed populations of dividing cells in blood.