Memory phenotype cd4 t cells undergoing rapid,nonburst-like,cytokine-driven proliferation can be distinguished from antigen-experienced memory cells

Memory phenotype (cd44 bright,cd25 negative) cd4 spleen and lymph node t cells (mp cells) proliferate rapidly in normal or germ-free donors,with brdu uptake rates of 6% to 10% per day and ki-67 positivity of 18% to 35%. the rapid proliferation of mp cells stands in contrast to the much slower proliferation of lymphocytic choriomeningitis virus (lcmv)-specific memory cells that divide at rates ranging from &1% to 2% per day over the period from 15 to 60 days after lcmv infection. anti-mhc class ii antibodies fail to inhibit the in situ proliferation of mp cells,implying a non-t-cell receptor (tcr)-driven proliferation. such proliferation is partially inhibited by anti-il-7rα antibody. the sequence diversity of tcrβ cdr3 gene segments is comparable among the proliferating and quiescent mp cells from conventional and germ-free mice,implying that the majority of proliferating mp cells have not recently derived from a small cohort of cells that expand through multiple continuous rounds of cell division. we propose that mp cells constitute a diverse cell population,containing a subpopulation of slowly dividing authentic antigen-primed memory cells and a majority population of rapidly proliferating cells that did not arise from naïve cells through conventional antigen-driven clonal expansion.