Co-stimulation of T cells results in distinct IL-10 and TNF-alpha cytokineprofiles dependent on binding to ICAM-1, ICAM-2 or ICAM-3

The LFA-1 adhesion molecule is involved in cell adhesion events of leukocyt es through binding to ICAM-1, ICAM-2 and ICAM-3. Whether binding to either of these ligands similarly affects co-stimulation of T cells and cytokine s ecretion is unknown. We demonstrated that LFA-1 co-stimulation under subopt imal concentrations of anti-CD3 monoclonal antibodies resulted in high, int ermediate and weak proliferation of T cells on ICAM-1, -2, and -3, respecti vely, which correlates with the distinct affinities of LFA-1 for these liga nds. Furthermore, we investigated whether binding to ICAM-1, -2 or -3 induc ed different cytokine profiles, thus regulating T helper cell function. Gra nulocyte-macrophage colony-stimulating factor and IFN-gamma were secreted i n high amounts, whereas IL-2, IL-4 and IL-5 could not be detected. Interest ingly, we observed that LFA-1/ICAM-1 co-stimulation of T cells resulted in high production of the Th2 cytokine IL-10 compared to ICAM-2 or ICAM-3 co-s timulation. In contrast, ICAM-2 and ICAM-3 induced a much stronger secretio n of the Th1 cytokine TNF-alpha compared to LFA-1/ICAM-1 induced co-stimula tion, despite the lower proliferation rate. These results demonstrate that besides facilitating cell adhesion, LFA-1 serves as a potent co-stimulatory molecule by inducing different cytokine patterns depending on the ligand b ound.