Characterization of intercellular adhesion molecule-1 (ICAM-1)-augmented degranulation by cytotoxic T cells. ICAM-1 and anti-CD3 must be co-localized for optimal adhesion and stimulation.
Purified intercellular adhesion molecule-1 (ICAM-1), a ligand of the LFA-1, was used to analyze the contribution of ICAM-1 to the activation of CTL. ICAM-1 facilitates degranulation when co-immobilized with substimulatory amounts of anti-CD3. This facilitated response is most likely mediated through LFA-1, since Abs to this molecule significantly inhibit the response, Interestingly, when ICAM-1 and anti-CD3 are immobilized on separate beads and presented to the CTL, no ICAM-1-enhanced degranulation is observed. The ICAM-1 and anti-CD3 must be immobilized on the same surface to augment the response, suggesting that ICAM-1 either does not transmit signals into the cell or it transmits a very localized signal, since the ICAM-1 and anti-CD3 must be juxtaposed. Consistent with this finding, we demonstrate that ICAM-1 does not induce tyrosine phosphorylation or a Ca(2+)-flux in the CTL clone, but does potentiate these responses when co-immobilized with substimulatory anti-CD3. Finally ICAM-1 and anti-CD3 must be immobilized on the same bead for stable adhesion of CTL to ICAM-1. When ICAM-1 and anti-CD3 are immobilized on separate beads, there is only a transient, low level of adhesion to the ICAM-1 beads. Taken together, these results suggest that LFA-1 is acting principally as an adhesion molecule, with respect to ICAM-1, in CTL and that this adhesion is regulated through the TCR complex.
Berg
N N
NN
Department of Immunology, University of Alberta, Edmonton, Canada.
Ostergaard
H L
HL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D015550:Cell Degranulation / Q000187:drug effects*; D002460:Cell Line; D018799:Intercellular Adhesion Molecule-1 / Q000302:isolation & purification / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D014443:Tyrosine; D002118:Calcium