Interleukin (IL)-16 is a
chemoattractant cytokine for CD4(+) leukocytes. Because delayed-type
hypersensitivity (DTH) reaction is mediated by T helper 1 (Th1) cells and CD4(+) T cells can be chemoattracted by
IL-16, we have investigated the involvement of
IL-16 in the DTH reaction. Immunohistochemical analysis revealed the
IL-16 expression in infiltrating cells and epithelial cells in the DTH footpads. The
IL-16 expression was also detected intracellularly in the infiltrating cells. In addition, markedly increased production of
IL-16 was detected in the DTH footpad extracts, but not in the control footpad extracts, by an
enzyme-linked
immunosorbent assay and also by Western blot analysis. The DTH footpad extracts exhibited a strong
chemoattractant activity toward splenic T cells, which was significantly inhibited by the inclusion of neutralizing
monoclonal antibody (mAb) against
IL-16 in the migration assay. Furthermore, treatment of sensitized mice in vivo with the anti-IL-16 neutralizing mAb significantly suppressed the footpad swelling induced by an
antigen challenge, together with decreased infiltration of leukocytes including not only CD4(+) T cells but also CD8(+) T cells and macrophages into the DTH footpads. Decreased production of
macrophage inflammatory protein 1alpha was also observed in the DTH footpad extracts by the mAb treatment. These results suggest that
IL-16 plays an important role in the recruitment of leukocytes-presumably including
antigen-specific Th1 cells, which secrete
cytokines and
chemokines mediating the following
hypersensitivity reaction after activation by the interaction with Langerhans cells carrying the
antigen-for the elicitation of DTH response. (Blood. 2000;95:2869-2874)