Memory phenotype CD4 T cells undergoing rapid, nonburst-like, cytokine-driven proliferation can be distinguished from antigen-experienced memory cells

PLoS Biol. 2011 Oct;9(10):e1001171. doi: 10.1371/journal.pbio.1001171. Epub 2011 Oct 11.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation / drug effects*
  • Cytokines / immunology*
  • Germ-Free Life
  • Histocompatibility Antigens Class II / immunology
  • Immunologic Memory / immunology*
  • Ki-67 Antigen / biosynthesis
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interleukin-7 / immunology


  • Cytokines
  • Histocompatibility Antigens Class II
  • Ki-67 Antigen
  • Mki67 protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain
  • Bromodeoxyuridine