INTERCELLULAR-ADHESION MOLECULE-3 (CD50) ON HUMAN EPIDERMAL LANGERHANS CELLS PARTICIPATES IN T-CELL ACTIVATION

Three different intercellular adhesion molecules (ICAMs) have been ide ntified acting as ligand for counter-receptor leukocyte-function-assoc iated antigen-1 (LFA-1) (CD11a/CD18). We have recently shown that ICAM -1 (CD54) is present on cultured human epidermal Langerhans cells but not on freshly isolated Langerhans cells, and that this molecule parti cipates in the generation of an antigen-specific T-cell response. ICAM -2 (CD102) was not involved because this molecule is expressed by neit her fresh nor cultured Langerhans cells. In this study, the presence o f ICAM-3 (CD50) on Langerhans cells was examined. Flow cytofluorometri c analysis demonstrated that ICAM-3 is strongly displayed by fresh Lan gerhans cells, and daily determinations showed that the level of this trypsin-resistant molecule remained nearly unchanged during in vitro c ulture for up to 4 d, indicating that Langerhans cells constitutively express this molecule. Analysis of RNA extracted from purified culture d Langerhans cells by means of reverse transcriptase-polymerase chain reaction demonstrated the presence of mRNA specific for ICAM-3. Antige n-specific T-cell responses triggered by Langerhans cells were dose-de pendently inhibited by anti-ICAM-3 if the antibody was added within th e first 16 h of T-cell stimulation. Simultaneous addition of anti-ICAM -1 and anti-ICAM-3 synergistically inhibited T-cell responses, althoug h a total block was never achieved. Pretreatment of Langerhans cells w ith anti-ICAM-3 resulted in a reduced T-cell response, whereas pretrea tment of T cells did not. These results suggest that ICAM-3 on Langerh ans cells, like ICAM-1, is functionally involved in the initiation of antigen-specific activation of T cells, but the expression of these tw o ICAMs on Langerhans cells is differently regulated.