Activated T cells induce expression of E-selectin in vitro and in an antigen-dependent manner in vivo.
E-selectin is an endothelial adhesion molecule for polymorphonuclear cells, monocytes and skin-homing T cells. We have analyzed whether murine T cells are able to induce expression of E-selectin in vitro and in vivo. Using models of inflammation in which T cells play either a significant or only a minor role, we compared induction of E-selectin between normal mice and mice lacking functional T cells (athymic nude mice). In irritant contact dermatitis, a model without a major role for T cells, E-selectin was transiently expressed within the first 24 h in both normal and nude mice. In experimental leishmaniasis (where specific T cells play an important role), a high expression of E-selectin was maintained for 48 h in normal mice, whereas in nude mice expression was only transient. However, reconstitution of nude mice with 10(8) T cells from draining lymph nodes (LN) of Leishmania-infected normal mice could restore sustained expression of E-selectin. Transfer of T lymphocytes from normal LN or from LN of mice sensitized to the contact allergen trinitrochlorobenzene (TNCB) did not have this effect. T cells from TNCB-sensitized mice, however, did induce sustained expression of E-selectin in nude mice when TNCB was applied locally; here, reconstitution with Leishmania-specific T cells had no effect. In vitro, T cells from infected or TNCB-sensitized normal mice increased expression of E-selectin on microvascular endothelial cells after 4 h of co-culture. T cells from untreated mice were less effective. Induction was dependent on direct cell-cell contact, but not on the action of interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha or interferon-gamma. We conclude that sensitized T cells induce sustained expression of E-selectin in vivo in an antigen-dependent manner. This novel way of regulation could be relevant for cell-mediated immunity and chronic disease. The mechanisms are unknown, but, as in vitro, might require direct cell-cell contact.
Sunderkötter
C
C
Department of Dermatology, University of Münster, Germany.
Steinbrink
K
K
Henseleit
U
U
Bosse
R
R
Schwarz
A
A
Vestweber
D
D
Sorg
C
C
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010853:Picryl Chloride / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000941:Antigens; D019040:E-Selectin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D010853:Picryl Chloride