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

• Published in: Immunity (Cambridge, Mass.) Mass.), 2007-06, Vol.26 (6), p.827-841
• Main Authors: Badovinac, Vladimir P., Haring, Jodie S., Harty, John T.
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; CD8-Positive T-Lymphocytes - immunology; CELLIMMUNO; Epitopes, T-Lymphocyte - immunology; Experiments; Hypotheses; Infections; Listeria monocytogenes; Listeriosis - immunology; Lymphocyte Activation; Lymphocytes; Mice; Mice, Transgenic; Ovalbumin - immunology; Phenotype; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Rodents; T cell receptors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2007.04.013

Adoptive-transfer experiments with relatively large input numbers (∼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 ∼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.