Co-stimulation of T cells results in distinct IL-10 and TNF-alpha cytokine profiles dependent on binding to ICAM-1, ICAM-2 or ICAM-3.
The LFA-1 adhesion molecule is involved in cell adhesion events of leukocytes 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 secretion is unknown. We demonstrated that LFA-1 co-stimulation under suboptimal concentrations of anti-CD3 monoclonal antibodies resulted in high, intermediate and weak proliferation of T cells on ICAM-1, -2, and -3, respectively, which correlates with the distinct affinities of LFA-1 for these ligands. Furthermore, we investigated whether binding to ICAM-1, -2 or -3 induced different cytokine profiles, thus regulating T helper cell function. Granulocyte-macrophage colony-stimulating factor and IFN-gamma were secreted in high amounts, whereas IL-2, IL-4 and IL-5 could not be detected. Interestingly, 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-stimulation. In contrast, ICAM-2 and ICAM-3 induced a much stronger secretion of the Th1 cytokine TNF-alpha compared to LFA-1/ICAM-1 induced co-stimulation, 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 bound.
Bleijs
D A
DA
Department of Tumor Immunology, University Hospital Nijmegen, The Netherlands.
de Waal-Malefyt
R
R
Figdor
C G
CG
van Kooyk
Y
Y
D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; C483616:ICAM3 protein, human; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10