Circulating activated platelets reconstitute lymphocyte homing and immunity in L-selectin-deficient mice.
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 beta2 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.
Diacovo
T G
TG
The Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA.
Catalina
M D
MD
Siegelman
M H
MH
von Andrian
U H
UH
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D000939:Epitopes; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D019041:L-Selectin / Q000097:blood / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000502:physiology; D008198:Lymph Nodes / Q000098:blood supply / Q000166:cytology / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D015539:Platelet Activation / Q000276:immunology*; D017713:Platelet Transfusion; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014699:Venules
D000939:Epitopes; D016169:Lymphocyte Function-Associated Antigen-1; D019041:L-Selectin