Initial T cell receptor transgenic cell precursor frequency dictates critical aspects of the CD8(+) T cell response to infection

Immunity. 2007 Jun;26(6):827-41. doi: 10.1016/j.immuni.2007.04.013. Epub 2007 Jun 7.

Abstract

Adoptive-transfer experiments with relatively large input numbers ( approximately 10(6)) of T cell receptor-transgenic (TCR-tg) T cells are widely used to model endogenous T cell responses to infection or immunization. We show that input numbers of naive TCR-tg T cells sufficient to squelch the endogenous response to the same epitope substantially alter the kinetics, proliferative expansion, phenotype, and efficiency of memory generation by the TCR-tg T cells in response to infection. Thus, responses from nonphysiologic input numbers of TCR-tg T cells fail to accurately mimic the endogenous T cell response. Importantly, seeding as few as approximately 10-50 TCR-tg T cells, which constitute a fraction of the endogenous repertoire, allowed vigorous proliferation and analysis of TCR-tg cells after infection in a scenario representing normal physiology for any individual TCR. These data strongly suggest that modeling the endogenous T cell response with TCR-tg cells will require every effort to approximate the endogenous precursor frequency.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Listeria monocytogenes*
  • Listeriosis / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Phenotype
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*

Substances

  • Epitopes, T-Lymphocyte
  • Receptors, Antigen, T-Cell
  • Ovalbumin