Bioluminescence-based visualization of CD4 T cell dynamics using a T lineage-specific luciferase transgenic model1
- Equal contributors
1 Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA
2 Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
3 Radiology Department, University of Alabama at Birmingham, Birmingham, Alabama, USA
4 Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
5 Department of Pathology, University of Alabama at Birmingham, BBRB 870, 845 19th St. S, Birmingham, Alabama, 35294, USA
BMC Immunology 2009, 10:44 doi:10.1186/1471-2172-10-44Published: 3 August 2009
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 in vivo biologic processes in real-time.
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.
The T-Lux mouse provides a novel, efficient model for tracking in vivo aspects of the CD4+ T cell response to antigen, providing an attractive approach for studies directed at immunotherapy or vaccine design.