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* Immunology Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta, Canada; and
Centre for Inflammatory Disease, Department of Medicine, Monash University, Victoria, Australia
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Canadian Institutes of Health Research and Canadian Institutes of Health Group. P.K. is an Alberta Heritage Foundation for Medical Research Scientist and a Canadian Research Chair recipient; M.U.N. is an Australian National Health and Medical Research Council CJ Martin Fellowship holder (284394) and is also an Alberta Heritage Foundation for Medical Research and Canadian Institutes of Health Research fellowship holder.
2 Address correspondence and reprint requests to Dr. Paul Kubes, Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive Northwest, Calgary, Alberta, T2N 4N1, Canada. E-mail address: pkubes{at}ucalgary.ca
3 Abbreviations used in this paper: CS, contact sensitivity; CP105,696, (+)-1-(3S,4R)-[3-(4-phenylbenzl)-4-hydroxychroman-7-yl]-cyclopentane carboxylic acid; 5-LO, 5-lipoxygenase; LTB4, leukotriene B4.
4 The online version of this article contains supplemental material.
This article has been cited by other articles:
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  M. U. Norman, J. Hwang, S. Hulliger, C. S. Bonder, J. Yamanouchi, P. Santamaria, and P. Kubes Mast Cells Regulate the Magnitude and the Cytokine Microenvironment of the Contact Hypersensitivity Response Am. J. Pathol., June 1, 2008; 172(6): 1638 - 1649. [Abstract] [Full Text] [PDF]
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