Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation

Immunity. 2010 Jul 23;33(1):128-40. doi: 10.1016/j.immuni.2010.06.014. Epub 2010 Jul 8.


Repetitive antigen stimulation by prime-boost vaccination or pathogen reencounter increases memory CD8(+) T cell numbers, but the impact on memory CD8(+) T cell differentiation is unknown. Here we showed that repetitive antigen stimulations induced accumulation of memory CD8(+) T cells with uniform effector memory characteristics. However, genome-wide microarray analyses revealed that each additional antigen challenge resulted in the differential regulation of several hundred new genes in the ensuing memory CD8(+) T cell populations and, therefore, in stepwise diversification of CD8(+) T cell transcriptomes. Thus, primary and repeatedly stimulated (secondary, tertiary, and quaternary) memory CD8(+) T cells differed substantially in their molecular signature while sharing expression of a small group of genes and biological pathways, which may constitute a core signature of memory differentiation. These results reveal the complex regulation of memory CD8(+) T cell differentiation and identify potential new molecular targets to dissect the function of memory cells generated by repeated antigen stimulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / genetics
  • Antigens / immunology*
  • Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Differentiation
  • Cells, Cultured
  • Gene Expression Profiling
  • Immunization, Secondary
  • Immunologic Memory
  • Immunophenotyping
  • Listeriosis / immunology*
  • Listeriosis / microbiology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism*
  • Lymphocyte Subsets / microbiology
  • Lymphocyte Subsets / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microarray Analysis
  • Ovalbumin / genetics
  • Ovalbumin / immunology*
  • Ovalbumin / metabolism
  • Transgenes / genetics


  • Antigens
  • Ovalbumin