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Updated: Jul 9, 2026
Imaging CD4 T Cell Interstitial Migration in the Inflamed Dermis
Published on: March 25, 2016
Multichannel fluorescence spinning disk microscopy reveals early endogenous CD4 T cell recruitment in contact
M Ursula Norman1, Sara Hulliger, Pina Colarusso
1Immunology Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta, Canada.
Insights
Contact sensitivity involves CD4 T cells, crucial for inflammation. This study reveals complement pathway
Area of Science:
- Immunology
- Dermatology
- Cellular Biology
Background:
- Contact sensitivity (CS) is a key T cell-mediated inflammatory model.
- CD4 T lymphocytes are essential for the late phase of CS.
- Early recruitment of CD4 T cells and mediator dynamics are hypothesized.
Purpose of the Study:
- To visualize and understand the very early effector events in contact sensitivity.
- To identify the role of specific cellular recruitment pathways in CS.
- To determine the importance of C5a receptor expression on immune cells.
Main Methods:
- Utilized spinning disk confocal microscopy for real-time visualization of cellular trafficking.
- Employed C5a receptor-deficient (C5aR-/-) mice and leukotriene B4 receptor antagonists.
- Quantified neutrophil and CD4 T cell recruitment and leukocyte infiltration post-hapten challenge.
Main Results:
- Observed rare CD4 T cell recruitment alongside predominant neutrophils.
- CD4 T cell recruitment was inhibited in C5aR-/- mice, but not by leukotriene B4 receptor antagonism.
- Neutrophil adhesion was reduced in both C5aR-/- and leukotriene B4 receptor antagonist-treated mice.
- Significant reduction in leukocyte infiltration and tissue damage in C5aR-/- mice.
- C5a receptor expression on T cells, not tissue cells, is critical for CS development.
Conclusions:
- Visualized early adaptive immune response events using advanced microscopy.
- Identified the complement pathway as essential for the recruitment of CD4 T cells in CS.
- Demonstrated the critical role of C5a receptor on T cells in contact sensitivity.
Abstract:
Contact sensitivity (CS) is one of the primary in vivo models of T cell-mediated inflammation. The presence of CS-initiating CD4 T lymphocytes at the time of challenge is essential for transfer and full development of the late phase CS inflammatory response. From this observation investigators have speculated that early recruitment of CD4 T cells to the site of challenge must occur. Moreover, there must be rapid synthesis/release and disappearance of an important mediator during the first hours after hapten challenge. Using spinning disk confocal microscopy, we observed the very early effector events of the immune response. Simultaneous, real-time visualization of predominant neutrophil and extremely rare CD4 T cell trafficking in the challenged skin vasculature was noted (one rolling CD4 T cell for every 10-18 rolling and adherent neutrophils). We demonstrate that neutrophil adhesion during the early CS response was reduced in C5a receptor-deficient (C5aR-/-) mice or leukotriene B4 receptor antagonist-treated mice, whereas CD4 T cell recruitment was only inhibited in C5aR-/- mice. In line with these observations, leukocyte infiltration and the associated tissue damage were significantly reduced in C5aR-/- mice but not in leukotriene B4 receptor antagonist-treated wild-type mice 24 h after challenge. C5a receptor expression on T cells and not on tissue resident cells was important for the development of a CS response. Thus, by using spinning disk confocal microscopy we visualized the early events of an adaptive immune response and identified the rare but essential recruitment of CD4 T cells via the complement pathway.
