The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/1/197/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 2, January 19, 1998 197-204

Articles

Circulating Activated Platelets Reconstitute Lymphocyte Homing and Immunity in L-selectin–Deficient Mice

Thomas G. Diacovo*,{ddagger},||, Michelle D. Catalina, Mark H. Siegelman, and Ulrich H. von Andrian*,§

From * The Center for Blood Research, the {ddagger} Department of Cardiology, and the § Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115; the || Division of Newborn Medicine, Department of Pediatrics, Tufts University School of Medicine, Boston, Massachusetts 02111; and the Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9069

Peripheral lymph nodes (PLN) are critical for immunologic memory formation in response to antigens that penetrate the skin. Blood-borne lymphocytes first encounter such antigens after they home to PLN through a multi-step adhesion process that is normally initiated by L-selectin (CD62L) in high endothelial venules (HEV). Since naive T cells can not enter PLN normally in L-selectin–deficient mice, a delayed type hypersensitivity response to cutaneously applied antigen cannot be mounted. In this study, we report that the administration of activated platelets into the systemic circulation of L-selectin knockout mice restores lymphocyte trafficking to PLN, and reconstitutes T cell–mediated immunity in response to a cutaneous antigen. These effects required platelet-expressed P-selectin that allows activated platelets to transiently form a bridge between lymphocytes and HEV, thereby enabling lymphocytes to undergo subsequent β2 integrin-dependent firm adhesion. These profound effects of platelet-mediated cell–cell interactions on lymphocyte trafficking and formation of immunologic memory may impact on a variety of autoimmune and inflammatory conditions.

Address corrrespondence to Dr. Ulrich H. von Andrian, The Center for Blood Research, 200 Longwood Ave., Boston, MA 02115. Phone: 617-278-3130; Fax: 617-278-3190; E-mail: uva{at}cbr.med.harvard.edu

M.H. Siegelman and U.H. von Andrian contributed equally to this work.

1 Abbreviations used in this paper: CHS, contact hypersensitivity; DNBS, 2,4-dinitro-benzene sulfonic acid; DNFB, 2,4-dinitrofluorobenzene; HEV, high endothelial venules; PLN, peripheral lymph nodes; PNAd, peripheral node addressin; PSGL-1, P-selectin glycoprotein ligand 1; TRAP, thrombin receptor-activating peptide; WBC, white blood cell.


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