Regulation of Langerhans cell function via blood borne factor(s).
Langerhans cells (LC) are epidermal dendritic cells that are functionally labile. Freshly obtained LC (fLC) readily activate allogeneic T cells, but they are incapable of activating autologous T cells; and even when pulsed with antigen, they fail to activate naive, antigen-specific T cells. When fLC are cultured for 2-3 days in the presence of keratinocytes, LC swiftly up-regulate surface expression of class I and II MHC molecules, and express de novo the co-stimulatory molecules B7 and ICAM-1. In addition to displaying enhanced ability to activate allogeneic T cells, cultured LC acquire the novel functional property of activating autologous T cells. It is believed that keratinocyte-derived GM-CSF is the primary driving force responsible for the conversion of fresh to cultured LC in vitro. However, in vivo administration of GM-CSF, either intracutaneously or systematically, fails to induce LC to undergo functional transformation in situ. Moreover, despite a high level of GM-CSF in the circulation, fLC from mice bearing GM-CSF-producing tumors display no ability to activate syngeneic T cells. These observations suggest that a homeostatic factor that antagonizes the effect of GM-CSF may be present in vivo. To test this possibility, we have examined the functional properties of LC prepared from mouse skin that had been explanted in vitro for 3 days. We found that the functional and phenotypic features of these cells closely resembled those of LC cultured in single cell suspension: the cells strongly expressed B7-1 and B7-2, and displayed enhanced expression of class II MHC molecules; they readily activated naive autologous T cells. Strikingly, when explants or suspensions of fresh epidermal cells were cultured in the presence of 10% mouse serum they failed to acquire syngeneic T cell activating properties; and surface up-regulation of Ia and de novo expression of B7 was inhibited. However, the cultured cells still expressed surface Ia and readily activated allogeneic naive T cells. If mouse serum was added only during the last 24 h of culture, the LC displayed full functional transformation. Human, rabbit and bovine serum showed no inhibitory effect on mouse LC. Our data suggest that mouse serum contains a factor (or factors) that inhibits, in a species-specific manner, epidermal LC from undergoing functional transformation in vitro, and this factor may maintain epidermal LC in the 'fresh' functional program in vivo.
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Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
Streilein
J W
JW
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D001769:Blood / Q000276:immunology; D002417:Cattle; D002450:Cell Communication; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000276:immunology / Q000502:physiology; D007801:Langerhans Cells / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor