P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflammed tissues.
When activated, T helper cells differentiate into one of two subsets, Th1 and Th2, characterized by distinct profiles of cytokine production. Th1 cells activate pro-inflammatory effector mechanisms involved in protection and autoimmunity, whereas Th2 cells induce humoral and allergic responses and downregulate local inflammation. Apart from differences in the repertoire of cytokines, no phenotypic attributes are established that distinguish the two subsets. Here we show that Th1 cells, but not Th2 cells, are able to bind to P-selectin and E-selectin. Moreover, only Th1 cells can efficiently enter inflamed sites in Th1-dominated models, such as sensitized skin or arthritic joints, but not in a Th2-dominated allergic response. Immigration of Th1 cells into inflamed skin can be blocked by antibodies against P- and E-selectin. These results provide evidence for adhesion mechanisms to distinguish between the two T helper subsets and mediate their differential trafficking. They indicate that selective recruitment is an additional level of regulation for both effector function profile and character of a local immune response.
Austrup
F
F
Abteilung für Immunologie, Medizinische Klinik, Universitätskrankenhaus Eppendorf, Hamburg, Germany.
Vestweber
D
D
Borges
E
E
Löhning
M
M
Bräuer
R
R
Herz
U
U
Renz
H
H
Hallmann
R
R
Scheffold
A
A
Radbruch
A
A
Hamann
A
A
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D019040:E-Selectin / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D019007:P-Selectin / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D019040:E-Selectin; D018836:Inflammation Mediators; D019007:P-Selectin