The Journal of Experimental Medicine
Keystone Symposia
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Published online 26 April 2004 doi:10.1084/jem.20032016
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 9, 1223-1234
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A Critical Temporal Window for Selectin-dependent CD4+ Lymphocyte Homing and Initiation of Late-Phase Inflammation in Contact Sensitivity

John M. Hwang1, Jun Yamanouchi2, Pere Santamaria2, and Paul Kubes1

1 Immunology Research Group, Department of Physiology and Biophysics and 2 Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada

Address correspondence to P. Kubes, Immunology Research Group, Dept. of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr. N.W., Calgary, Alberta, T2N 4N1 Canada. Phone: (403) 220-8558; Fax: (403) 283-1267; email: pkubes{at}ucalgary.ca

Contact sensitivity (CS) is an inflammatory disorder characterized by early and late phases of leukocyte recruitment. We used a noninvasive intravital microscopy technique allowing for the direct visualization of leukocyte rolling and adhesion on blood vessel endothelium. By blocking specific adhesion molecules, we elucidated the molecular mechanisms mediating early leukocyte recruitment to be E- and P-selectin and demonstrated that leukocyte recruitment in the late phase had a different adhesive profile (mainly {alpha}4-integrin). Complete blockade of E- and P-selectin within the first 2 h of leukocyte–endothelial cell interactions (but not later) eliminated selectin-independent leukocyte recruitment at 24 h. Despite the predominance of neutrophils in the early phase, specific elimination of CD4+ lymphocytes in the early phase eliminated the late response. CD4+ lymphocytes homed to skin via E- and P-selectin within the early phase and induced the late phase response. Addition of these same CD4+ lymphocytes 2 h after antigen challenge was too late for these cells to home to the skin and induce late phase responses. Our data clearly demonstrate that the antigen-challenged microenvironment is only accessible to CD4+ lymphocytes for the first 2 h, and that this process is essential for the subsequent recruitment of other leukocyte populations in late phase responses.

Key Words: delayed hypersensitivity • contact dermatitis • neutrophils • vascular cell adhesion molecule-1 • CD4+ T lymphocytes

The online version of this article contains supplemental material.

Abbreviation used in this paper: CS, contact sensitivity.


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