The role of ICAM-1/LFA-1 and VCAM-1/VLA-4 interactions on T helper 2 cytokine production by lung T cells of Toxocara canis-infected mice

In order to study the effect of costimulatory signals on T helper type 2 (Th2) cytokine production, monoclonal antibodies (mAb) against cell adhesion molecules (CAM) were added to cells in culture obtained from the lungs of Toxocara canis (Tc)-infected mice followed by the determination of interleukin-5 (IL-5) and IL-4 in the supernatants of the culture. ES-stimulated IL-5 production in the supernatant of total lung cells was reduced by 25% when anti-intercellular adhesion molecule-1 (anti-ICAM-1) mAb, anti-CD11a mAb, or both anti-ICAM-1 and anti-CD11a mAb together were added to the culture. The addition of anti-CD18 mAb had no effects. Anti-vascular cell adhesion molecule-1 (anti-VCAM-1) mAb addition also reduced IL-5 production by 60%, although the addition of anti-very late activation antigen-4, (anti-VLA-4) mAb or both anti-VCAM-1 and anti-VLA-4 mAb together were less effective. In the case of anti-CD3 mAb stimulation, similar effects of mAb to CAM were observed. In contrast, IL-4 production induced by anti-CD3 mAb was reduced more markedly by the addition of either anti-ICAM-1 or anti-CD11a mAb than the combination of anti-VCAM-1 and anti-VILA-4 mAb. Similar effects of mAb to CAM were observed on the production of IL-5 and IL-4 by CD4(+) T cells purified using a fluorescence-activated cell sorter. Coincubation with adherent cells was necessary for the significant production of IL-5 and IL-4 by CD4(+) T cells. These results suggest that the VCAM-1/VLA-4 interaction is more important for IL-5 production by CD4(+) T cells in the lungs of Tc-infected mice, and that the ICAM-1/lymphocyte function-associated antigen-1 interaction is more important for the production of IL-4.