Stimulation of naïve T-cell adhesion and immunological synapse formation by chemokine-dependent and -independent mechanisms.
Bromley SK., Dustin ML.
Chemokines adsorbed to the cell surface play an important role in the initial interactions of T cells with endothelial cells, and may also have a role in T-cell interactions with dendritic cells. Therefore, we examined the effect of surface-adsorbed chemokines on the interaction of naïve murine splenic T cells with supported bilayers containing intercellular adhesion molecule (ICAM)-1, or with bone marrow-derived cultured dendritic cells in the presence and absence of relevant MHC-peptide complexes. Naïve T cells formed immunological synapses, defined as a ring of lymphocyte function associated (LFA)-1-ICAM-1 interactions surrounding a central cluster of MHC-peptide complexes, on supported planar bilayers containing ICAM-1 and relevant MHC-peptide complexes. Chemokines stimulated an increase in the percentage of naïve cells that adhered to ICAM-1, but did not increase the average number of LFA-1-ICAM-1 interactions in the contact area. In contrast, relevant MHC-peptide complexes resulted in a small increase in the proportion of interacting T cells, but stimulated an 8-fold increase in the number of LFA-1-ICAM-1 interactions in each contact formed. Naïve T cells displayed a significant basal adhesion to bone marrow dendritic cells that was further increased when relevant chemokines were adsorbed to the dendritic cell surface. However, basal and antigen-stimulated T-cell adhesion to dendritic cells was not sensitive to pertussis toxin. Thus, there are chemokine-independent mechanisms that initiate adhesion between T cells and dendritic cells.