IL-12 has various effects on T cells and natural killer cells including the stimulation of lymphokine production, especially of IFN-γ. IL-12-mediated antitumor effect requires T cell infiltration into tumor masses. However, it remains to be examined whether IL-12 affects the expression of VLA-4/LFA-1 on T cells or modulates the capacity of these adhesion molecules.
In the present study, the expression levels of VLA-4 and LFA-1 on T cells present in lymphoid organs and tumor masses from tumor-bearing mice were analyzed with and without IL-12 treatment in various (two IL-12-curable and two incurable) tumor models. The results showed that significantly enhanced expression of both VLA-4 and LFA-1 (VLA-4
intLFA-1
int) was observed in some T cells from spleens of IL-12- untreated tumor-bearing mice only in IL-12-curable models. In these models, IL-12 treatment increased the number of VLA-4
intLFA-1
int T cells in splenic populations as well as the number of tumorinfiltrating T cells. In IL-12-incurable models, VLA- 4
intLFA-1
int T cells were not generated in spleens, and tumor-infiltrating T cells were hardly harvested even after IL-12 treatment. The inhibition of the VLA-4-VCAM-1 and LFA-1-ICAM-1 interactions with anti-VCAM-1 and anti-ICAM-1 monoclonal antibodies resulted in the prevention of T cell migration, and tumor regression was induced following IL-12 treatment. The results suggested that the capacity of IL-12 to promote T cell migration correlates with the induction of VLA-4
intLFA-1
int T cells prior to IL-12 treatment.
抄録全体を表示