Lymphocyte recruitment in delayed-type hypersensitivity. The role of IFN-γ

Lymphocytes are recruited out of the blood into delayed-type hypersensitivity (DTH) reactions, but the factors controlling their migration are poorly understood. Our previous studies have shown that IFN-α/β, its inducers, and T cell lymphokines can induce lymphocyte migration into the skin after intradermal injection. The present studies were designed to determine the effect of rIFN-γ, IL-1, and anti-IFN-γ on lymphocyte recruitment into DTH. Small peritoneal exudate lymphocytes, which preferentially migrate to inflammatory sites, were labelled with ¹¹¹In and injected i.v. into rats. The intradermal injection of IFN-γ stimulated the migration of these lymphocytes into the skin. IL-1 induced very little migration by itself, but enhanced the effect of IFN-γ. Kinetic analysis demonstrated that the migration of lymphocytes to IFN-γ was rapid, with a peak at 6 h, whereas migration into a DTH reaction was minimal for the first 8 h and reached a peak 24 h after intradermal injection. Polyclonal rabbit anti-IFN-γ anti-serum, and a Mab to IFN-γ, DB-2, could almost completely block lymphocyte migration induced by IFN-γ. Furthermore, DB-2 inhibited lymphocyte recruitment into DTH reactions by 50 to 90%. This Mab did not affect migration in response to IFN-α/β, although it partially inhibited the response to polyI:C. The effect of IFN-γ on lymphocyte recruitment was not specific for small peritoneal exudate lymphocytes, because both spleen T cells and lymph node cells migrated in response to IFN-γ and DB-2 inhibited the recruitment of splenic T cells to DTH. Thus, IFN-γ is a potent stimulator of lymphocyte migration into the skin and a major mediator of lymphocyte recruitment into DTH.