Bioluminescence-based visualization of CD4 T cell dynamics using a T lineage-specific luciferase transgenic model¹

• Main Authors: Zinn Kurt R, Chaudhuri Tandra R, Dugger Kari J, Chewning Joseph H, Weaver Casey T
• Format: Article
• Language: English
• Published: BMC 2009-08-01
• Series: BMC Immunology
• Online Access: http://www.biomedcentral.com/1471-2172/10/44

<p>Abstract</p> <p>Background</p> <p>Rapid clonal expansion of T cells occurs in response to antigenic challenges. The kinetics of the T cell response has previously been described using tissue-based studies performed at defined time points. Luciferase bioluminescence has recently been utilized for non-invasive analysis of <it>in vivo </it>biologic processes in real-time.</p> <p>Results</p> <p>We have created a novel transgenic mouse model (T-Lux) using a human CD2 mini-gene to direct luciferase expression specifically to the T cell compartment. T-Lux T cells demonstrated normal homing patterns within the intact mouse and following adoptive transfer. Bioluminescent signal correlated with T cell numbers in the whole body images as well as within specific organ regions of interest. Following transfer into lymphopenic (RAG2^-/-) recipients, homeostatic proliferation of T-Lux T cells was visualized using bioluminescent imaging. Real-time bioluminescent analysis of CD4⁺T cell antigen-specific responses enabled real-time comparison of the kinetics and magnitude of clonal expansion and contraction in the inductive lymph node and tissue site of antigen injection. T cell expansion was dose-dependent despite the presence of supraphysiologic numbers of OVA-specific OT-II transgenic TCR T-Lux T cells. CD4⁺T cells subsequently underwent a rapid (3–4 day) contraction phase in the draining lymph node, with a delayed contraction in the antigen delivery site, with bioluminescent signal diminished below initial levels, representing TCR clonal frequency control.</p> <p>Conclusion</p> <p>The T-Lux mouse provides a novel, efficient model for tracking <it>in vivo </it>aspects of the CD4⁺T cell response to antigen, providing an attractive approach for studies directed at immunotherapy or vaccine design.</p>