Beta2 integrins are required for skin homing of primed T cells but not for priming naive T cells.
Beta2 integrins are of critical importance for leukocyte extravasation through vascular endothelia and for T cell activation. To elucidate the role of beta2 integrins in T cell-mediated immune responses, allergic contact dermatitis (ACD), irritant dermatitis, and delayed-type hypersensitivity (DTH) were assessed in mice lacking the beta2 integrin subunit, CD18. ACD and DTH responses, but not edema formation, were severely suppressed in CD18(-/-) mice. Extravasation of CD18(-/-) T cells into eczematous skin lesions was greatly impaired, whereas migration of Langerhans cell precursors and dendritic cells was normal in CD18(-/-) mice. CD18(-/-)lymph nodes (LNs) contained an abnormal population of CD3(-)CD44(high) lymphocytes and showed evidence of widespread T cell activation. T cells from regional LNs of sensitized CD18(-/-) mice proliferated in response to hapten challenge, and subcutaneous injection of sensitized syngeneic LN cells directly into ears of hapten-challenged naive recipients restored the defective ACD in CD18(-/-) mice, suggesting that CD18 is not required for priming of naive T cells but is indispensable for T cell extravasation. Thus, a dysfunction of T cells, in addition to granulocytes, may contribute to the pathophysiology of leukocyte adhesion deficiency type I, which arises from mutations in the human CD18 gene.
Grabbe
Stephan
S
Department of Dermatology, University of Münster, Münster, Germany. grabbe@uni-muenster.de
Varga
Georg
G
Beissert
Stefan
S
Steinert
Meike
M
Pendl
Gunther
G
Seeliger
Stephan
S
Bloch
Wilhelm
W
Peters
Thorsten
T
Schwarz
Thomas
T
Sunderkötter
Cord
C
Scharffetter-Kochanek
Karin
K
D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D018821:CD18 Antigens