Bioluminescence-based visualization of CD4 T cell dynamics using a T lineage-specific luciferase transgenic model.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Chewning
Joseph H
JH
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. joechewn@uab.edu
Dugger
Kari J
KJ
Chaudhuri
Tandra R
TR
Zinn
Kurt R
KR
Weaver
Casey T
CT
D019264:Adoptive Transfer; D000818:Animals; D018801:CD2 Antigens / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D054443:Cell Migration Assays; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D008156:Luciferases / Q000037:antagonists & inhibitors / Q000235:genetics; D008163:Luminescent Measurements; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D018801:CD2 Antigens; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D008156:Luciferases