Initial T Cell Receptor Transgenic Cell Precursor Frequency Dictates Critical Aspects of the CD8+ T Cell Response to Infection

• DOI: 10.1016/j.immuni.2007.04.013
• Publication Date: 2007-06-08T16:54:36Z
• Authors: Vladimir P. Badov...; Jodie S. Haring; John T. Harty
• Keywords: Ovalbumin; Immunology; Receptors, Antigen, T-Cell; Epitopes, T-Lymphocyte; Mice, Transgenic; CD8-Positive T-Lymphocytes; Lymphocyte Activation; Adoptive Transfer; Listeria monocytogenes; Mice; 03 medical and health sciences; Infectious Diseases; Phenotype; 0302 clinical medicine; CELLIMMUNO; Immunology and Allergy; Animals; Listeriosis

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.