Intercellular adhesion molecule-3 (CD50) on human epidermal Langerhans cells participates in T-cell activation

Three different intercellular adhesion molecules (ICAMs) have been identified acting as ligand for counter-receptor leukocyte-function-associated 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 participates in the generation of an antigen-specific T-cell response. ICAM-2 (CD102) was not involved because this molecule is expressed by neither fresh nor cultured Langerhans cells. In this study, the presence of ICAM-3 (CD50) on Langerhans cells was examined. Flow cytofluorometric analysis demonstrated that ICAM-3 is strongly displayed by fresh Langerhans cells, and daily determinations showed that the level of this trypsin-resistant molecule remained nearly unchanged during in vitro culture for up to 4 d, indicating that Langerhans cells constitutively express this molecule. Analysis of RNA extracted from purified cultured Langerhans cells by means of reverse transcriptase-polymerase chain reaction demonstrated the presence of mRNA specific for ICAM-3. Antigen-specific T-cell responses triggered by Langerhans cells were dose-dependently inhibited by anti-ICAM-3 if the antibody was added within the first 16 h of T-cell stimulation. Simultaneous addition of anti-ICAM-1 and anti-ICAM-3 synergistically inhibited T-cell responses, although a total block was never achieved. Pretreatment of Langerhans cells with anti-ICAM-3 resulted in a reduced T-cell response, whereas pretreatment of T cells did not. These results suggest that ICAM-3 on Langerhans cells, like ICAM-1, is functionally involved in the initiation of antigen-specific activation of T cells, but the expression of these two ICAMs on Langerhans cells is differently regulated.